Pharmacokinetics Of Lansoprazole Research Articles

Nanostructured lipid carriers for transdermal delivery of acid labile lansoprazole

The aim of this study was to develop nanostructured lipid carriers (NLCs) for transdermal delivery of acid-labile lansoprazole (LPZ). The drug loading, particle size, zeta potential, thermal behavior and stability of NLCs were evaluated. The particle size of NLCs was in the range of 90−210nm and the zeta potential was −61.9 to +3.2mV dependent of the compositions. Stearylamine (SA) prevented lansoprazole degradation and maintained drug stable in NLCs. The anionic sodium dodecyl sulfate (SDS) adsorbed on the lipid surface and formed complex with cationic SA to prevent NLCs aggregation. The effects of type (e.g., isopropyl myristate (IPM), menthol) and concentration (e.g., 1.25, 2.50, 3.75%w/w) of enhancers on penetration of lansoprazole NLC hydrogels were investigated in vitro using Wistar rat skin. The steady-state flux of lansoprazole NLC hydrogel containing 3.75% IPM was the highest which was enhanced by 2.7 folds as compared to enhancer-free NLC hydrogel. In vivo pharmacokinetics of lansoprazole following transdermal delivery of NLC hydrogel showed that the elimination of drug was significantly reduced and the mean residence time of drug was prominently prolonged as compared to intravenous drug solution (p<0.005). The accumulation of drug in the skin and continuous penetration of drug through the skin accounted for the maintenance of drug concentration for at least 24h.

Effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites in rats

abstract The aim of this study was to evaluate the effects of caffeine, tea polyphenol and daidzein on the pharmacokinetics of lansoprazole and its metabolites. Rats were intragastrically administered caffeine (30 mg·kg-1, once per day), tea polyphenol (400 mg·kg-1, once per day) or daidzein (13.5 mg·kg-1, once per day) for 14 days, followed by an intragastric administration of lansoprazole (8 mg·kg-1) on the 15th day. The plasma concentrations of lansoprazole and its two primary metabolites, 5-hydroxylansoprazole and lansoprazole sulfone, were determined by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Tea polyphenol significantly elevated the Area Under the Curve (AUC) of lansoprazole from 680.29 ± 285.99 to 949.76 ± 155.18 μg/L.h and reduced that of lansoprazole sulfone from 268.82 ± 82.37 to 177.72 ± 29.73 μg/L.h. Daidzein increased the AUC of lansoprazole from 680.29 ± 285.99 to 1130.44 ± 97.6 μg/L.h and decreased that of lansoprazole sulfone from 268.82 ± 82.37 to 116.23 ± 40.14 μg/L.h. The pharmacokinetics of 5-hydroxylansoprazole remained intact in the presence of tea polyphenol or daidzein. Caffeine did not affect the pharmacokinetics of lansoprazole and its metabolites. The results imply that tea polyphenol and daidzein may inhibit the in vivo metabolism of lansoprazole by suppressing CYP3A.

Effects of genetic polymorphisms of CYP2C19*2/*3 and MDR1 C3435T on the pharmacokinetics of lansoprazole in healthy Chinese subjects.

To evaluate the influence of CYP2C19*2/*3 and MDR1 C3435T polymorphisms on the pharmacokinetics of lansoprazole (LPZ) in healthy Chinese subjects. All 24 subjects were from a study of bioequivalence. Plasma concentrations of LPZ were determined by liquid chromatography/mass spectrometry. Cytochrome P450 (CYP) 2C19*2/*3 and multidrug resistance transporter gene 1 (MDR1) C3435T of the subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Significant differences were found in the area under the concentration-time curve from predose to T (AUC(0-T)), area under the concentration-time curve from predose to infinity (AUC(0-∞), t(1/2)), and apparent oral clearance (CL/F) of LPZ between CYP2C19 extensive metabolizers and intermediate metabolizers (p < 0.05). The AUC(0-T), AUC(0-∞), maximum plasma concentration, and CL/F of LPZ were significantly different between subjects with the MDR1 C3435T C/C, C/T, and T/T polymorphisms (p < 0.05). CYP2C19*2/*3 and MDR1 C3435T polymorphisms are important determinants of LPZ pharmacokinetics.

Pharmacokinetics of lansoprazole and its main metabolites after single and multiple intravenous doses in healthy Chinese subjects

The aim of the study was to evaluate and compare the pharmacokinetics of lansoprazole (LPZ) and its main metabolites, 5'-hydroxy lansoprazole (HLPZ) and lansoprazole sulfone (LPZS), after single and multiple intravenous (i.v.) doses of LPZ in healthy Chinese subjects. Twelve subjects (six males and six females) were given a single dose of LPZ by i.v. infusion on day 1, and multiple doses from day 2 to day 6. Blood samples were collected at designated time points for analysis of plasma concentrations of LPZ, HLPZ and LPZS by an LC-MS/MS method. LPZ was generally well tolerated in healthy Chinese subjects. After single and multiple i.v. doses of 30 mg LPZ, the C max values of LPZ, HLPZ and LPZS were 1490 ± 290 and 1450 ± 280, 175 ± 71 and 154 ± 56, and 51.3 ± 82.9 and 74.1 ± 158.7 ng/mL, with the AUC0-t values 3280 ± 2550 and 4260 ± 3880, 381 ± 128 and 389 ± 111, and 389 ± 1204 and 700 ± 2255 ng h/mL, respectively. The t 1/2 and CL values of LPZ after single and multiple i.v. doses were 1.48 ± 1.03 and 2.19 ± 1.03 h, and 11.67 ± 4.49 and 9.56 ± 4.08 L/h, respectively. Compared with the pharmacokinetics of LPZ after a single dose, t 1/2 increased markedly, CL decreased significantly and AUC increased by over 20 % after multiple doses. The results indicated that there was drug accumulation of LPZ after multiple i.v. doses, and there was no gender-related difference in pharmacokinetics of LPZ and its two metabolites.

Pharmacokinetics of lansoprazole and its main metabolites after single intravenous doses in healthy Chinese subjects

The aim of the study was to evaluate the pharmacokinetics (PK) of lansoprazole (LPZ) and its main metabolites 5′-hydroxy lansoprazole (HLPZ) and lansoprazole sulphone (LPZS) after single intravenous (i.v.) doses of LPZ in healthy Chinese subjects, and the relationship between the cytochrome P450 (CYP) 2C19 phenotypes and the plasma concentrations of LPZS at the time-points in the elimination phase of LPZ.Twelve subjects were given lansoprazole by i.v. infusion. Blood samples were collected at designated time points up to 24 h. Plasma concentrations of LPZ, HLPZ and LPZS were quantified by a selective and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method.After single i.v. doses of 15, 30 and 60 mg LPZ, Cmax and area under the plasma concentration-time curve (AUC0-t) of LPZ were 725 ± 151, 1480 ± 190, 3130 ± 480 µg·L−1 and 1690 ± 1210, 3630 ± 2530, 8080 ± 4550 µg·h·L−1, respectively. LPZ was generally well tolerated in healthy Chinese subjects, and displayed linear PK in the range of 15–60 mg.There were significant differences in the elimination of LPZ and the formation of LPZS between the single CYP2C19 poor metabolizer (PM) and the CYP2C19 extensive metabolizers (EM). The concentration of LPZS at the time-points in the elimination phase of LPZ could be monitored for CYP2C19 phenotyping. As a probe drug for CYP2C19 phenotyping, LPZ for injection might be more suitable than LPZ oral formulations.

Influence of Cytochrome P450 2C19 on the pharmacokinetics of lansoprazole administered by single and successive intravenous infusion in healthy Chinese volunteers

This study aimed to explore the effect of CYP2C19 polymorphisms on the pharmacokinetics of lansoprazole administered by single and successive intravenous (iv) infusions in healthy Chinese volunteers. A total of 30 subjects, including 20 extensive metabolizers (EMs) and 10 poor metabolizers (PMs) were recruited and randomly assigned to three groups receiving doses of 15, 30 and 60 mg. All subjects received a single dose of lansoprazole during a 60-min period, and only the 30 mg dose group continued to receive the same dose iv for the next seven days (twice daily). Plasma concentrations of lansoprazole were monitored by high performance liquid chromatography (HPLC) at the following times: 15, 30, 45, 60, 75, 105, 165, 225, 300, 390, 480, 600 and 720 min after lansoprazole administration. After a single intravenous infusion in the three groups, AUC, Cmax and t½ were significantly higher in PMs than in EMs, while total clearance (Cltotal) in PMs was significantly lower than that in EMs. Mean AUC and Cmax ratios in EMs and PMs were 2.1:1 and 1.4:1, respectively. After repeated doses of 30 mg, the AUC, Cmax, and t½ increased significantly, while the Cltotal decreased significantly in EMs. Mean AUC and Cmax ratios in EMs and PMs amounted to 2.2:1.4 and 1.5:1.2, respectively. Lansoprazole displays a linear increase in AUC and Cmax over a dose range of 15-60 mg, and these were dependent on individual CYP2C19 status.

Effect of Fluoxetine on the Pharmacokinetics of Lansoprazole

Fluoxetine is an inhibitor of the main metabolizing enzymes of lansoprazole and could influence the pharmacokinetics of lansoprazole. The changes in lansoprazole pharmacokinetics could have clinical significance concerning the safety of the therapy. The aim of this study was to evaluate the pharmacokinetic interaction between fluoxetine and lansoprazole in healthy subjects. A dose of lansoprazole 30 mg, alone or in combination with fluoxetine 60 mg, was administered to 18 healthy male subjects in a two-treatment study design, separated by an 8-day period in which fluoxetine alone was administered as a single oral daily dose. Plasma concentrations of lansoprazole were determined during a 12-hour period following drug administration. Lansoprazole plasma concentrations were determined by a validated liquid chromatography-mass spectrometry method. The pharmacokinetic parameters of lansoprazole were calculated using non-compartmental analysis. In the two periods of treatment, the mean maximum plasma concentration (C(max)) values were 817 ng/mL (lansoprazole alone) and 1370 ng/mL (lansoprazole in combination with fluoxetine after pre-treatment with fluoxetine for 8 days) [p < 0.0001]. The observed area under the plasma concentration-time curve (AUC) from time zero to time of last measurable concentration values were 2400 and 6220 ng · h/mL (p < 0.0001), respectively, and the AUC from time zero to infinity values were 2480 and 7290 ng · h/mL (p < 0.0001), respectively. The time to reach C(max) values were 2.72 and 2.64 hours, respectively. The elimination rate constant from the central compartment values were 0.50 and 0.21 h-1, respectively (p < 0.0001). The elimination half-life values were 1.47 and 3.56 hours (p < 0.0001), respectively, and the mean residence times were 4.0 and 6.9 hours (p < 0.0001), respectively. The data demonstrate a pharmacokinetic interaction between fluoxetine and lansoprazole and suggest that the observed interaction may be clinically significant, although its clinical relevance has yet to be confirmed.

Effects of CYP2C19 polymorphism on the pharmacokinetics of lansoprazole and its main metabolites in healthy Chinese subjects

The aim of the study was to determine the pharmacokinetics of lansoprazole and its main metabolites (5′-hydroxy lansoprazole and lansoprazole sulphone) after administration of enteric-coated tablet in healthy Chinese subjects classified by CYP2C19 genotypes, and evaluate the effects of CYP2C19 genotypes on the pharmacokinetics of the three compounds.A single oral dose of 30 mg lansoprazole was administrated to 24 healthy Chinese male volunteers in different CYP2C19 genotype groups. Blood samples were collected from pre-dose up to 14-h post-dose. Plasma concentration of lansoprazole and its main metabolites were quantified by liquid chromatography-tandem mass spectrometry.CYP2C19 polymorphism had significant effects on the pharmacokinetics of lansoprazole and its main metabolites. The differences in the pharmacokinetics between CYP2C19 extensive metabolizers (Ems) (homo-EMs and hete-EMs) and PMs were more significant for lansoprazole sulphone than for 5′-hydroxy lansoprazole.The results indicate that the monitoring of lansoprazole and its main metabolites in plasma at the time-points in the elimination phase for lansoprazole could reflect the activity of CYP2C19. Simultaneously monitored with lansoprazole sulphone, lansoprazole might be a useful probe drug for CYP2C19.

The effect of CYP2C19 activity on pharmacokinetics of lansoprazole and its active metabolites in healthy subjects

Context: Lansoprazole is a gastric proton-pump inhibitor and has been demonstrated to be effective in the treatment of various peptic diseases. The effects of CYP2C19 activity on the pharmacokinetics of lansoprazole and its active metabolites in Chinese subjects have not previously been evaluated.Objective: The study aimed to evaluate the effects of CYP2C19 activity in healthy Chinese volunteers.Materials and methods: Twenty-two healthy volunteers were recruited for an open trial and received a single dose of 30 mg lansoprazole. Using a validated LC-MS/MS method, we measured the plasma concentrations of lansoprazole, 5-hydroxylansoprazole, and lansoprazole sulfone. The genotype of CYP2C19 was identified by polymerase chain reaction (PCR) analysis of single nucleotide polymorphisms (SNPs). Subjects were genotypically classified into the following three groups on the basis of PCR-SNP analysis for CYP2C19: homozygous EM (hmEM) group, heterozygous EM (htEM) group, and PM group. To test differences in pharmacokinetic parameters among the three groups, analysis of variance (ANOVA) after log-transformation of data was used.Results and conclusion: Our results indicated that there were significant differences (p < 0.001) between the hmEM and PM groups, between the htEM and PM groups, and between the hmEM and htEM groups in Cmax, AUC0–t, and AUC0–inf of lansoprazole and lansoprazole sulfone. There were also significant differences (p < 0.001) between the hmEM and PM groups, and between the htEM and PM groups in Cmax of 5-hydroxylansoprazole.

Effect of CYP2C19 *2 and *17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians

The influence of CYP2C19 on the kinetics and dynamics of omeprazole, lansoprazole and rabeprazole has been studied in Japanese subjects. * It has been suggested that subjects with *1/*1 genotype might need stronger acid suppression than *1/*2 and *2/*2 subjects. This suggestion comes from data in Japanese subjects and has not been confirmed in Caucasians. * Furthermore, a novel CYP2C19 mutation, *17, which mainly occurs in Caucasians has been discovered. This mutation has been associated with clinical failure, but its relevance for therapy with PPIs has not been studied yet. In this study, the influence of CYP2C19 on both the pharmacokinetics and dynamics in Caucasian subjects after single and repeated dosing has been investigated. * This is the first study showing that Caucasian subjects with *1/*1 and *1/*17 mutations need stronger acid-inhibition. In this study three proton pump inhibitors (omeprazole, lansoprazole and pantoprazole, in different doses) were studied of which pantoprazole had not been studied before in this setting, not even in Japanese. To investigate the impact of CYP2C19 mutations *2-*6 and *17 on acid-inhibition and pharmacokinetics of lansoprazole (L15), omeprazole (O10, O20) and pantoprazole (P40) in Caucasians. CYP2C19 genotyping for *2-*6 and *17 mutations was assessed in subjects who were H. pylori negative in two randomized crossover trials. The influence of CYP2C19 mutations on single and repeated administration of L15 and O10 (study A) and O20 and P40 (study B) was investigated. Pharmacokinetics and the cumulative percentage of time with intragastric pH above 4 (% > pH 4) were assessed on day 1 and 6. For study A CYP2C19 genotyping found five *1/*1, four *1/*2, one *1/*17 and one *2/*17. For study B the results were six *1/*1, two *1/*2, six *1/*17, one *2/*2 and one *2/*17. For all PPIs AUC was highest in *2/*2 and lowest in *1/*17. On day 1, all PPIs significantly increased percentage >pH 4 compared with baseline. *1/*1 genotype showed no significant acid-inhibition after L15, O10 and O20. *1/*17 genotype showed no significant acid-inhibition after O20 and P40. *1/*2 genotype showed significant acid-inhibition after L15 and O10. On day 6, all four PPIs showed significantly increased acid-inhibition. *1/*1 and *1/*17 showed a significantly increased percentage > pH 4 after treatment with O20 and P40. However, in *1/*1 subjects percentage > pH 4 was not significantly increased after L15 and O10. *1/*2 genotype showed a significant acid-inhibitory effect after repeated dosing with L15 and O10. Caucasian subjects with *1/*1 and *1/*17 genotype need stronger acid-suppression therapy, especially during the first days of treatment or with on-demand therapy.

Age-Dependent Pharmacokinetics of Lansoprazole in Neonates and Infants

Evidence suggests that age may affect the pharmacokinetics of lansoprazole in pediatric patients, but little information is available in neonates and infants. To determine the pharmacokinetics of lansoprazole in neonates and infants <1 year of age with gastroesophageal reflux disease (GERD)-associated symptoms. Two single- and repeated-dose, randomized, open-label, multicenter studies were conducted. Studies involved a pretreatment period of 7 or 14 days, a dose administration period of 5 days, and a follow-up period of 30 days for adverse events collection. The studies were conducted in both hospital and private clinic settings. The studies were performed in 24 neonates (aged <or=28 days) and 24 infants (aged >28 days, but <1 year) with GERD-associated symptoms diagnosed by medical history and the clinical judgment of the treating physician. Participants received lansoprazole 0.5 or 1.0 mg/kg/day (neonates) or 1.0 or 2.0 mg/kg/day (infants) for 5 days. Plasma pharmacokinetic parameters on dose administration day 1 were calculated, and plasma concentrations on day 5 were obtained. The pharmacokinetics of lansoprazole were approximately dose proportional. After a single dose in neonates, the mean maximum plasma concentrations (C(max)) were 831 and 1672 ng/mL, and the mean area under the plasma concentration-time curve (AUC) values were 5086 and 9372 ng . h/mL for lansoprazole doses of 0.5 and 1.0 mg/kg, respectively. The time to C(max) (t(max)) [3.1 hours] and harmonic mean terminal elimination half-life (t((1/2))) [2.8 hours] were slightly longer in neonates receiving 0.5 mg/kg than the t(max) (2.6 hours) and t((1/2)) (2.0 hours) values observed in neonates receiving 1.0 mg/kg. Mean oral clearance (CL/F) was identical for the two doses (0.16 L/h/kg). After a single 1.0 or 2.0 mg/kg dose in infants, the lansoprazole C(max) values were 959 and 2087 ng/mL and the mean AUC values were approximately 2203 and 5794 ng . h/mL, respectively. The mean t(max) and mean t((1/2)) were 1.8 hours and 0.8 hours, respectively, for both doses (1.0 or 2.0 mg/kg), while mean CL/F was 0.71 and 0.61 L/h/kg, respectively. In both patient groups, mean plasma concentrations on day 5 were similar to day 1 concentrations. No clinically meaningful accumulation was observed following 5 days' dose administration. Plots of lansoprazole pharmacokinetics against chronologic age showed that dose-normalized C(max), t((1/2)), and AUC were two, three, and five times higher, respectively, in study participants aged <or=10 weeks than in study participants aged >10 weeks-1 year. Lansoprazole was well tolerated in all patients. The pharmacokinetics of lansoprazole in pediatric patients are age dependent, with those aged <or=10 weeks showing higher plasma exposure and lower plasma clearance than those aged >10 weeks-1 year. Thus, pediatric patients aged <or=10 weeks require a lower dose of lansoprazole than pediatric patients aged >10 weeks to achieve similar plasma exposure.

Influence of ABCB1 C3435T polymorphism on the pharmacokinetics of lansoprazole and gastroesophageal symptoms in Japanese renal transplant recipients classified as CYP2C19 extensive

Lansoprazole and tacrolimus are substrates of ATP binding cassette (ABC) transporters such as P-glycoprotein (ABCBI/multidrug resistance 1) and cytochrome P450 (CYP). The purpose of this study was to investigate the implication of the ABCB1 C3435Tpolymorphism on the pharmacokinetics of (R)-lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus. 24 recipients who were CYP2C19 EMs were studied. Oral administration of 30 mg lansoprazole was started 2 days before transplantation. On Day 2 before and Day 28 after transplantation, the plasma concentrations of (R)-lansoprazole and tacrolimus were measured. Pretransplantation, there were no significant differences in the pharmacokinetic parameters of (R)-lansoprazole between the 3 ABCBI C3435T genotypes. However, after renal transplantation, the peak plasma concentration (Cma ) and area under the plasma concentration-time curve (AUCO-24) of (R)-lansoprazole in patients with the ABCB1 C3435T C allele significantly increased, but not in patients with the TT genotype. These pharmacokinetic variations in (R)-lansoprazole did not influence the AUC of tacrolimus. There were no significant differences in the frequency of gastroesophageal symptoms among the three ABCB] C3435Tgenotypes. (R)-lansoprazole concentrations significantly increased in CYP2C19 extensive metabolizers with the ABCB1 C3435T C allele, but not TT genotype, after renal transplantation. However, the clinical relevance of this observation may be minor because these pharmacogenetic changes were not associated with the occurrence of gastroesophageal complications.

Lack of Significant Effect of Grapefruit Juice on the Pharmacokinetics of Lansoprazole and Its Metabolites in Subjects With Different CYP2C19 Genotypes

The Journal of Clinical PharmacologyVolume 45, Issue 6 p. 690-694 Lack of Significant Effect of Grapefruit Juice on the Pharmacokinetics of Lansoprazole and Its Metabolites in Subjects With Different CYP2C19 Genotypes Dr Tsukasa Uno PhD, Dr Tsukasa Uno PhD Department of Pharmacy, Hirosaki University Hospital, Hirosaki, JapanSearch for more papers by this authorDr Norio Yasui-Furukori MD PhD, Corresponding Author Dr Norio Yasui-Furukori MD PhD Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, JapanAddress for reprints: Norio Yasui-Furukori, MD, PhD, Department of Neuropsychiatry, Hirosaki University, School of Medicine, Hirosaki 036-8562, Japan.Search for more papers by this authorDr Takenori Takahata MD, PhD, Dr Takenori Takahata MD, PhD Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, Japan First Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, JapanSearch for more papers by this authorDr Kazunobu Sugawara PhD, Dr Kazunobu Sugawara PhD Department of Pharmacy, Hirosaki University Hospital, Hirosaki, JapanSearch for more papers by this authorDr Tomonori Tateishi MD, PhD, Dr Tomonori Tateishi MD, PhD Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, JapanSearch for more papers by this author Dr Tsukasa Uno PhD, Dr Tsukasa Uno PhD Department of Pharmacy, Hirosaki University Hospital, Hirosaki, JapanSearch for more papers by this authorDr Norio Yasui-Furukori MD PhD, Corresponding Author Dr Norio Yasui-Furukori MD PhD Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, JapanAddress for reprints: Norio Yasui-Furukori, MD, PhD, Department of Neuropsychiatry, Hirosaki University, School of Medicine, Hirosaki 036-8562, Japan.Search for more papers by this authorDr Takenori Takahata MD, PhD, Dr Takenori Takahata MD, PhD Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, Japan First Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, JapanSearch for more papers by this authorDr Kazunobu Sugawara PhD, Dr Kazunobu Sugawara PhD Department of Pharmacy, Hirosaki University Hospital, Hirosaki, JapanSearch for more papers by this authorDr Tomonori Tateishi MD, PhD, Dr Tomonori Tateishi MD, PhD Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, JapanSearch for more papers by this author First published: 07 March 2013 https://doi.org/10.1177/0091270005275430Citations: 11Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume45, Issue6June 2005Pages 690-694 RelatedInformation

Effects of clarithromycin on lansoprazole pharmacokinetics betweenCYP2C19genotypes

AimsLansoprazole is a substrate of CYP2C19 and CYP3A. The aim of this study was to compare the inhibitory effects of clarithromycin, an inhibitor of CYP3A on the metabolism of lansoprazole betweenCYP2C19genotypes.MethodsA two‐way randomized double‐blind, placebo‐controlled crossover study was performed. Eighteen volunteers, of whom six were homozygous extensive metabolizers (EMs), six were heterozygous EMs and six were poor metabolizers (PMs) for CYP2C19, received two 6‐day courses of either clarithromycin 800 mg or placebo daily in a randomized fashion with a single oral dose of lansoprazole 60 mg on day 6 in all cases. Plasma concentrations of lansoprazole and its metabolites, 5‐hydroxylansoprazole and lansoprazole sulphone were monitored up to 24 h after dosing.ResultsDuring placebo administration, the mean AUC(0, ∞) of lansoprazole in homozygous EMs, heterozygous EMs and PMs were 4652 (95% CI, 2294, 7009) ng ml−1 h, 8299 (4784, 11814) ng ml−1 h and 25293 (17643, 32943) ng ml−1 h (P &lt; 0.001), respectively. Clarithromycin treatment significantly increasedCmaxby 1.47‐fold, 1.71‐fold and 1.52‐fold and AUC(0, ∞) of lansoprazole by 1.55‐fold, 1.74‐fold, and 1.80‐fold in these genotype groups, respectively, whereas elimination half‐life was prolonged only in PMs. The clarithromycin‐mediated percent increase in pharmacokinetic parameters such asCmax, AUC(0, ∞) or elimination half‐life did not differ between the threeCYP2C19genotypes.ConclusionsThe present study indicates that there are significant drug interactions between lansoprazole and clarithromycin in allCYP2C19genotype groups probably through CYP3A inhibition. The bioavailability of lansoprazole might, to some extent, be increased through inhibition of P‐glycoprotein during clarithromycin treatment.

Comparison of the pharmacokinetics of lansoprazole 15- and 30-mg sachets for suspension versus intact capsules

Objective: The pharmacokinetic profiles of single doses of lansoprazole 15- and 30-mg sachets for suspension were compared with those of corresponding doses of lansoprazole oral capsules. Methods: Healthy adult male and female subjects were randomized (1:1 ratio) into 2 Phase 1, open-label, single-dose, 2-sequence, 2-period complete crossover studies. In the first study, each subject received 1 lansoprazole 15-mg sachet mixed with water and 1 lansoprazole 15-mg oral capsule; in the second study, each subject received 1 lansoprazole 30-mg sachet mixed with water and 1 lansoprazole 30-mg oral capsule. Administration of the 2 formulations was separated by a washout period of ≥7 days. Blood samples were collected before and after each administration to assess the pharmacokinetic parameters of lansoprazole and bioequivalence between suspension and capsule. Results: Thirty-six subjects (19 males, 17 females) with a mean (SD) age of 32.0 (9.6) years and mean (SD) body weight of 68.6 (10.5) kg received lansoprazole 15 mg. Thirty-six subjects (22 males, 14 females) with a mean (SD) age of 38.0 (8.3) years and mean (SD) body weight of 75.1 (9.7) kg received lansoprazole 30 mg. The pharmacokinetic parameters of the 15- and 30-mg lansoprazole sachets for suspension were similar to those of the corresponding doses of the oral capsules. The mean (SD) values for C max and AUC from time 0 to infinity (AUC 0—∞ for the lansoprazole 15-mg sachet (591.9 [242.3] ng/mL and 1614 [2065] ng·h/mL, respectively) did not differ significantly from those for the lansoprazole 15-mg capsules (578.6 [275.2] ng/mL and 1620 [2290] ng·h/mL, respectively). These parameters also did not differ significantly between the lansoprazole 30-mg sachet and 30-mg capsule: mean (SD) C max, 1103 (428.3) and 1077 (465.6) ng/mL, respectively; mean (SD) AUC 0—∞, 2655 (1338) and 2669 (1311) ng·h/mL, respectively. The 90% Cls for C max and AUC 0—∞ ratios were contained within the 0.80 to 1.25 equivalence range, supporting bioequivalence. Conclusions: These findings suggest that the 15- and 30-mg lansoprazole sachets for suspension are bioequivalent to the corresponding doses of oral capsules. The sachet for suspension may provide an alternative route of administration to patients who have difficulty swallowing solid oral formulations.

Effects of Fluvoxamine on Lansoprazole Pharmacokinetics in Relation to CYP2C19 Genotypes

Lansoprazole is a substrate of CYP2C19 and CYP3A4. The aim of this study was to compare the inhibitory effects of fluvoxamine, an inhibitor of CYP2C19, on the metabolism of lansoprazole between CYP2C19 genotypes. Eighteen volunteers--of whom 6 were homozygous extensive metabolizers (EMs), 6 were heterozygous EMs, and 6 were poor metabolizers (PMs) for CYP2C19--received three 6-day courses of either daily 50 mg fluvoxamine or placebo in a randomized fashion with a single oral 60-mg dose of lansoprazole on day 6 in all cases. Plasma concentrations of lansoprazole and its metabolites, 5-hydroxylansoprazole and lansoprazole sulfone, were monitored up to 24 hours after the dosing. During placebo administration, there was a significant difference in the area under the plasma concentration-time curve from time 0 to infinity (AUC(0-infinity)) of lansoprazole between CYP2C19 genotypes. Fluvoxamine treatment increased AUC(0-infinity) of lansoprazole by 3.8-fold (P < .01) in homozygous EMs and by 2.5-fold (P < .05) in heterozygous EMs, whereas no difference in any pharmacokinetic parameters was found in PMs. There was a significant difference in the fluvoxamine-mediated percentage increase in the AUC(0-infinity) of lansoprazole between CYP2C19 genotypes. The present study indicates that there are significant drug interactions between lansoprazole and fluvoxamine in EMs. CYP2C19 is predominantly involved in lansoprazole metabolism in EMs.

Effect of Water Intake on Pharmacokinetics of Lansoprazole from Past Disintegrating Tablet in Human Subjects

Lansoprazole fast disintegrating tablet (LFDT) has been developed as a multiple unit formulation to increase the QOL of patients, i.e., easy intake without water. However, there is a possibility that patients intake LFDT in accordance with clarithromycin and amoxicillin with water. To study the effect of water on the absorption of lansoprazole (LPZ), the study was carried out using human volunteers. After selected by phenotype of LPZ metabolism, extensive metabolizers (EMs) of LPZ were used in this study. Twelve healthy male EMs intook LFDT containing 30 mg LPZ with 150 mL of water and without-water, i.e., with saliva, to study the pharmacokinetics of LPZ from the gastrointestinal tract by a cross-over manner with one-week washout period under fasted condition in the morning. The mean AUC(0-24s) were 2004.4+/-973.6 ng.h/mL in without-water experiment and 2018.5+/-1159.6 ng.h/mL in the case of with-water experiment. Mean C(maxs) were 851.9+/-450.8 ng/mL in without-water experiment and 830.8+/-456.8 ng/mL in with-water experiment, respectively. ANOVA was applied to the log-transformed AUC(0-24) and C(max) values. The 90% two sided confidence intervals for log-transformed AUC(0-24) was 0.78-1.22 and that for log-transformed C(max) was 0.67-1.37, respectively. By comparing these pharmacokinetic parameters, we may state that there was no significant difference between the two administration modes.

Pharmacokinetics of lansoprazole, amoxicillin and clarithromycin after simultaneous and single administration

Pharmacokinetics of lansoprazole, amoxicillin and clarithromycin after simultaneous and single administration

Pharmacokinetics of lansoprazole with multiple oral and intravenous doses

Pharmacokinetics of lansoprazole with multiple oral and intravenous doses

Pharmacokinetics of lansoprazole in adolescent patients with gastroesophageal reflux disease (GERD)

' =p <0.05 PGEz and TxB2 in the pouch exudate and in the stomach of the animals was measured by ELISA. Indomethacin dose-dependentl y caused a significant inhibition of synthesis of PGEz and TxB zboth at the inflammatory site and in the stomach and induced formation of gastric erosions. On the contrary , celocoxib or darbufel one treated animals did not develop any gastric damage and inhibition of PGEz and TxBz synthesis was observed mainly in the pouch exudate. The degree of inhibition of PGEz and TxBz synthesis observed at a dose of 10 mg/kg for the three drugs tested is reported in the table below (Average :!: St. Err.)(n). In conclusion, our data suggest s that darbufelone has a celocox ib-like profile and the preferent ial inhibition of synthesis of arachidonic acid metabolites at the inflammatory site but not in the stomach, could explain the low risk of developing gastrointestinal damage.