Pharmacokinetics Of Amlodipine Research Articles

Pharmacokinetic Evaluation of Amlodipine Tablet Compared with Norvask® Tablet in Healthy Indonesian Adults

This study objective to evaluate the pharmacokinetics of Amlodipine 10 mg Produced by PT. Tropica Mas Pharmaceuticals compared to Norvask® 10 mg Tablet Produced by PT. Pfizer Indonesia, in healthy Indonesian Adults through bioequivalence study. This study is utilized by randomized, single-dose, openlabel, two-way cross-over design with a washout period 14 days and fasting. This study involved 18 subjects, with only 17 subjects included in the statistical analysis, because 1 subject withdrew due to diarrhoea in the 2nd period. Plasma samples were collected 17 times for 72-hour per period. Amlodipine concentrations were measured using LCMS/MS. Bioequivalence was determined by value of 90% confidence interval (CI) with α = 5.00% within the range of 80.00–125.00% for AUC and Cmax. The geometric mean ratios (90% CI) of the test drug vs. the innovator drug were 101.67% (97.16 – 106.39) for AUC0-t and 100.46% (95.00 – 106.23) for Cmax. Based on the result, the test drug is bioequivalent to the comparator drug.

The Impact of Paediatric Obesity on Drug Pharmacokinetics: A Virtual Clinical Trials Case Study with Amlodipine.

The incidence of paediatric obesity continues to rise worldwide and contributes to a range of diseases including cardiovascular disease. Obesity in children has been shown to impact upon the plasma concentrations of various compounds, including amlodipine. Nonetheless, information on the influence of obesity on amlodipine pharmacokinetics and the need for dose adjustment has not been studied previously. This study applied the physiologically based pharmacokinetic modelling and established a paediatric obesity population to assess the impact of obesity on amlodipine pharmacokinetics in children and explore the possible dose adjustments required to reach the same plasma concentration as non-obese paediatrics. The difference in predicted maximum concentration (Cmax) and area under the curve (AUC) were significant between children with and without obesity across the age group 2 to 18 years old when a fixed-dose regimen was used. On the contrary, a weight-based dose regimen showed no difference in Cmax between obese and non-obese from 2 to 9 years old. Thus, when a fixed-dose regimen is to be administered, a 1.25- to 1.5-fold increase in dose is required in obese children to achieve the same Cmax concentration as non-obese children, specifically for children aged 5 years and above.

Фармакокинетика амлодипина у пациентов с артериальной гипертензией

Aim. To evaluate the pharmacokinetics of amlodipine in patients with arterial hypertension. Design. Open cohort study. Materials and methods. The study included 183 patients, 98 of them with uncontrolled arterial hypertension and 85 with controlled hypertension. All patients regularly took any two antihypertensive drugs (AHD) (lisinopril, amlodipine, valsartan, metoprolol) in combination with indapamide for a month. In the morning, fasting, before taking AHD and 2 hours after taking amlodipine, venous blood samples were taken from all patients to test the concentration of the analyte using high-performance liquid chromatography with tandem mass spectrometry. Results. In terms of the main concomitant diseases, the patients of the two groups were comparable to each other. Only angina pectoris (p = 0.02) and overweight (p = 0.02) were statistically significantly more common in the pressure–controlled group, and less often — grade 2 obesity (p = 0.002) and acute cerebrovascular accident (p = 0.05). The daily dose of amlodipine in patients with controlled hypertension was significantly (13.9%) lower (p < 0.05) than in participants with uncontrolled hypertension. Both the steadystate concentration of amlodipine and the concentration 2 hours after administration in patients with uncontrolled hypertension were not statistically significantly different from those in patients with controlled hypertension (p > 0.05). In 65.6% of patients with uncontrolled and in 49.4% with controlled hypertension, the concentration of amlodipine was within the therapeutic range (p = 0.03), in 5.2% and 16.5%, respectively, it was above the therapeutic range (p = 0.016), in 29.2% and 34.1%, respectively, — below the therapeutic range (p > 0.05). Conclusion. Conducting therapeutic drug monitoring and assessing the pharmacokinetics of amlodipine in clinical practice may be useful to improve the effectiveness and safety of therapy. Keywords: arterial hypertension, antihypertensive drugs, amlodipine, high-performance liquid chromatography with tandem mass spectrometry.

Impact of Cumin and Green Tea on Amlodipine Pharmacodynamics and Pharmacokinetics in Hypertensive Rats

The main purpose of the current research was to determine the impact of cumin and green tea on the pharmacodynamics and pharmacokinetics of amlodipine in hypertensive rats. Wistar rats were given 40 mg/kg of L-NAME orally every day for two weeks in order to induce hypertension. The groups treated with herbs received L-NAME with a daily oral dose of cumin (200 mg/kg) and green tea (200 mg/kg), respectively. After the treatment for 14 days, blood pressure was measured at specific intervals using a tail-cuff BP-measurement device for 24 h. For oral pharmacokinetics of amlodipine (single dose, 1 mg/kg), the blood samples were collected at predetermined intervals up to 24 h, and plasma samples were analyzed using UPLC-LC MS/MS. In comparison to the hypertensive control group, green tea and cumin significantly decreased systolic and diastolic blood pressures, as well as mean arterial pressures. Green tea has demonstrated a more prominent effect on pharmacodynamic of amlodipine compared to cumin. The rats treated with amlodipine, cumin + amlodipine, and green tea + amlodipine exhibited AUC0-t of 38.85 ± 14.8 ng h/mL, 52.05 ± 10.2 ng h/mL, and 114.73 ± 24.94 ng h/mL, respectively. In addition, it has been observed that co-administration of green tea and cumin increases the Cmax and T1/2 of amlodipine. The results indicated a potential interaction between amlodipine and the investigated herbs in hypertensive rats. Hence, precautions should be taken while concurrently administrating amlodipine with the investigated herbs.

Genetic Variation in CYP2D6 and SLC22A1 Affects Amlodipine Pharmacokinetics and Safety.

Amlodipine is an antihypertensive drug with unknown pharmacogenetic biomarkers. This research is a candidate gene study that looked for associations between amlodipine pharmacokinetics and safety and pharmacogenes. Pharmacokinetic and safety data were taken from 160 volunteers from eight bioequivalence trials. In the exploratory step, 70 volunteers were genotyped for 44 polymorphisms in different pharmacogenes. CYP2D6 poor metabolizers (PMs) showed higher half-life (t1/2) (univariate p-value (puv) = 0.039, multivariate p-value (pmv) = 0.013, β = -5.31, R2 = 0.176) compared to ultrarapid (UMs), normal (NMs) and intermediate metabolizers (IMs). SLC22A1 rs34059508 G/A genotype was associated with higher dose/weight-corrected area under the curve (AUC72/DW) (puv = 0.025; pmv = 0.026, β = 578.90, R2 = 0.060) compared to the G/G genotype. In the confirmatory step, the cohort was increased to 160 volunteers, who were genotyped for CYP2D6, SLC22A1 and CYP3A4. In addition to the previous associations, CYP2D6 UMs showed a lower AUC72/DW (puv = 0.046, pmv = 0.049, β = -68.80, R2 = 0.073) compared to NMs, IMs and PMs and the SLC22A1 rs34059508 G/A genotype was associated with thoracic pain (puv = 0.038) and dizziness (puv = 0.038, pmv = 0.014, log OR = 10.975). To our knowledge, this is the first work to report a strong relationship between amlodipine and CYP2D6 and SLC22A1. Further research is needed to gather more evidence before its application in clinical practice.

Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling.

For children, a special population who are continuously developing, a reasonable dosing strategy is the key to clinical therapy. Accurate dose predictions can help maximize efficacy and minimize pain in pediatrics. Methods: This study collected amlodipine pharmacokinetics (PK) data from 236 Chinese male adults and established a physiological pharmacokinetic (PBPK) model for adults using GastroPlus™. A PBPK model of pediatrics is constructed based on hepatic-to-body size and enzyme metabolism, used similar to the AUC0-∞ to deduce the optimal dosage of amlodipine for children aged 1–16 years. A curve of continuous administration for 2-, 6-, 12-, 16-, and 25-year-olds and a personalized administration program for 6-year-olds were developed. Results: The results show that children could not establish uniform allometric amplification rules. The optimal doses were 0.10 mg·kg−1 for ages 2–6 years and −0.0028 × Age + 0.1148 (mg/kg) for ages 7–16 years, r = 0.9941. The trend for continuous administration was consistent among different groups. In a 6-year-old child, a maintenance dose of 2.30 mg was used to increase the initial dose by 2.00 mg and the treatment dose by 1.00 mg to maintain stable plasma concentrations. Conclusions: A PBPK model based on enzyme metabolism can accurately predict the changes in the pharmacokinetic parameters of amlodipine in pediatrics. It can be used to support the optimization of clinical treatment plans in pediatrics.

Effect of Hibiscus sabdariffa and Zingiber officinale on pharmacokinetics and pharmacodynamics of amlodipine.

To study the effect of Zingiber officinale and Hibiscus sabdariffa on pharmacokinetics and pharmacodynamics of amlodipine. Hypertension was induced in rats (SBP 173.2 ± 1.7 mmHg, mean, 1-24 h). Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and heart rate (HR) of group-I (amlodipine treated), group-II (Z. officinale, and Z. officinale + amlodipine) and group-III (H. sabdariffa, and H. sabdariffa + amlodipine) animals were measured by "tail-cuff system". Pharmacokinetics of amlodipine with and without herbs (Z. officinale or H. sabdariffa) was also investigated. Z. officinale as well as H. sabdariffa decreased the SBP, DBP and MBP. Concurrent treatment with Z. officinale + amlodipine (SBP 129.4 ± 4.5) or H. sabdariffa + amlodipine (SBP 130.4 ± 3.9) showed higher decrease in BP (mean, 1-24h), than individually administered amlodipine (SBP 149.5 ± 2.4) or Z. officinale (SBP 150.2 ± 3.1) or H. sabdariffa (SBP 139.1 ± 1.2). These herbs also influenced the Cmax, AUC0-t, and Tmax of amlodipine. H. sabdariffa increased AUC0-t of amlodipine from 81.8 ± 14.7 to 125.0 ± 10.6 (ng h/mL). Simultaneous administration of Z. officinale or H. sabdariffa with amlodipine, improves its pharmacodynamic response.

Effect of Nigella sativa and Fenugreek on the Pharmacokinetics and Pharmacodynamics of Amlodipine in Hypertensive Rats.

The present article is related to in-vitro and in-vivo herb-drug interaction studies. This study aimed to investigate the effect of Nigella sativa and fenugreek on the pharmacodynamics and pharmacokinetics of amlodipine. Hypertensive rats of group-I were treated with amlodipine and rats of group-II and III were treated with N. sativa, and N. sativa + amlodipine and fenugreek, and fenugreek + amlodipine, respectively. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) of group-I, II and III rats were measured by the "tail-cuff system". N. sativa, as well as fenugreek, reduced the SBP, DBP and MBP. Simultaneously, administration of fenugreek + amlodipine or N. sativa + amlodipine showed better control of BP. Individually, fenugreek, as well as N. sativa, showed a surprising reduction in the heart rate. There was no remarkable effect of any of these two herbs on Cmax, AUC0-t, Kel, and terminal elimination half-life of amlodipine, but fenugreek altered the Tmax of amlodipine significantly, from 2 ± 1.2h in control to 7.2 ± 1.7h in fenugreek treated group, probably by delaying the absorption. Results of pharmacodynamics and pharmacokinetics studies suggested that simultaneous administration of fenugreek or N. sativa with amlodipine improved the pharmacological response of amlodipine in hypertensive rats, though there was no remarkable change in pharmacokinetic parameters (Cmax, Kel, elimination t1/2, and AUC0-t).

Effects of cytochrome P450 oxidoreductase genotypes on the pharmacokinetics of amlodipine in healthy Korean subjects.

BackgroundThe aim of this study was to investigate the effects of P450 oxidoreductase (POR) genetic polymorphisms on the pharmacokinetic parameters of amlodipine.MethodsAfter a single 10‐mg dose of amlodipine administration, 25 healthy male subjects completed genotyping for 12 single nucleotide polymorphisms (SNPs) of the POR genes, cytochrome P450 (CYP)3A4 g.25343G>A (CYP3A4*1G), and CYP3A5 g.12083G>A (CYP3A5*3). Stratified analysis and in silico analysis to predict the possible effects of given variants on splicing were performed.ResultsThe maximum blood concentration (Cmax) of amlodipine in carriers of g.57332T>C and g.56551G>A SNPs of the POR gene was statistically significantly different. In addition, T‐allele carriers of g.57332T>C had a 21% higher Cmax than those with the CC genotype (p = .007). Subjects who carried the wild‐type g.56551G>A allele also had a 1.12‐fold significantly higher Cmax than subjects with mutant‐type homozygous carriers (p = .033). In stratified analyses, g.57332T>C was significantly associated with a 1.3‐fold increase in Cmax value in T‐allele carriers compared with subjects with the CC genotype in CYP3A4 and CYP3A5 expressers. POR g.57332T>C increased the score above the threshold in both ESEfinder 3.0 and HSF 3.1.ConclusionThis study identified a novel SNP of the POR gene, which affected amlodipine metabolism and may reduce interindividual variation in responses to amlodipine.

Effects of curcumin on the pharmacokinetics of amlodipine in rats and its potential mechanism

Context Hyperlipidaemia and hypertension are often treated together with curcumin and amlodipine. It is necessary to investigate the drug-drug interaction between curcumin and amlodipine. Objective The interaction between curcumin and amlodipine was investigated in rats and with rat liver microsomes. Methods The pharmacokinetics of amlodipine (1 mg/kg) was investigated in rats with or without curcumin pre-treatment (2 mg/kg), six rats in each group. The metabolic stability of amlodipine was investigated with rat liver microsomes. Results Curcumin significantly increased the C max (26.19 ± 2.21 versus 17.80 ± 1.56 μg/L), AUC(0-t) (507.27 ± 60.23 versus 238.68 ± 45.59 μg·h/L), and t1/2 (14.69 ± 1.64 versus 11.43 ± 1.20 h) of amlodipine (p < 0.05). The metabolic stability of amlodipine was significantly increased with the half-life time in rat liver microsomes increased from 34.23 ± 3.33 to 44.15 ± 4.12 min, and the intrinsic rate decreased from 40.49 ± 3.26 to 31.39 ± 2.78 μL/min/mg protein. Discussion and conclusions These results indicated that drug–drug interaction might appear during the co-administration of curcumin and amlodipine. The potential mechanism may be due to the inhibition of CYP3A4 by curcumin. Thus, this interaction should be given special attention in the clinic and needs further experiments to characterize the effect in humans.

Effects of atorvastatin on pharmacokinetics of amlodipine in rats and its potential mechanism

Atorvastatin combined with amlodipine (ALDP) can efficiently treat the hypertension with coronary heart disease. However, the drug-drug interaction between atorvastatin and ALDP are still unknown.This study investigates the effects of atorvastatin on the pharmacokinetics of ALDP in rats and clarifies its main mechanism.The pharmacokinetic profiles of oral administration of ALDP (1 mg/kg) in Sprague-Dawley rats, with or without pretreatment of atorvastatin (1.5 mg/kg/d for 7 d) were investigated. The effects of atorvastatin on the metabolism of ALDP were also investigated using rat liver microsomes.The results showed that atorvastatin could significantly increase the peak plasma concentration (from 18.28 ± 2.65 to 24.13 ± 1.96 ng/mL) and decrease the oral clearance (from 4.57 ± 1.15 to 1.79 ± 0.28 L/h/kg) of ALDP. In the rat liver microsome systems, the intrinsic clearance rate of ALDP was decreased by the pretreatment with atorvastatin (39.26 ± 2.1 vs. 33.24 ± 3.3 μL/min/mg protein).Those results indicated that atorvastatin could significantly affect the pharmacokinetic of ALDP, via inhibiting the metabolism of ALDP in rats.

Effects of Danshen tablets on pharmacokinetics of amlodipine in rats

Context: Danshen tablets (DST), an effective traditional Chinese multi-herbal formula, are often combined with amlodipine (ALDP) for treating coronary heart disease.Objective: This study investigated the effects of DST on the pharmacokinetics of ALDP and the potential mechanism.Materials and methods: The pharmacokinetics of ALDP (1 mg/kg) in male Sprague–Dawley rats (n = 6), with or without pretreatment of DST (100 mg/kg for 7 d), were investigated using LC-MS/MS. The effects of DST on the metabolic stability of ALDP were also investigated using rat liver microsomes (RLM).Results: The results indicated that Cmax (16.25 ± 2.65 vs. 22.79 ± 2.35 ng/ml), AUC(0–t) (222.87 ± 59.95 vs. 468.32 ± 69.87 n gh/ml), and t1/2 (10.60 ± 1.05 vs. 14.15 ± 1.59 h) decreased significantly when DST and ALDP were co-administered, which suggested that DST might influence the pharmacokinetic behaviour of ALDP when they are co-administered. The metabolic stability of ALDP was also decreased (23.6 ± 4.7 vs. 38.9 ± 5.2) with the pretreatment of DST.Discussion and conclusions: This study indicated that DST could accelerate the metabolism of ALDP in RLM and change the pharmacokinetic behaviours of ALDP. Accordingly, these results showed that the herb–drug interaction between DST and ALDP might occur when they were co-administered. Therefore, the clinical dose of ALDP should be increased when DST and ALDP are co-administered.

Effect Of epigallocatechin-3-gallate on the pharmacokinetics of amlodipine in rats

This study investigates the effect of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea, on the pharmacokinetics of amlodipine in rats.The pharmacokinetics of orally administered amlodipine (1 mg/kg) with or without EGCG pretreatment (30 mg/kg/day for 10 days) were investigated. Plasma concentrations of amlodipine were determined by using a sensitive and reliable liquid chromatography with tandem mass spectroscopy (LC-MS/MS) method. The effects of EGCG on the metabolic stability of amlodipine were investigated by using rat liver microsome incubation systems.The results indicated that when the rats were pretreated with EGCG, the Cmax of amlodipine increased from 16.32 ± 2.57 to 21.44 ± 3.56 ng/mL (p < 0.05), the Tmax decreased from 5.98 ± 1.25 to 4.01 ± 1.02 h (p < 0.05), and the AUC0–t increased from 258.12 ± 76.25 to 383.34 ± 86.95 μg h L−1 (p < 0.05), which suggested that the pharmacokinetic behavior of amlodipine was affected after oral co-administration of EGCG. Additionally, the metabolic half-life was prolonged from 31.3 ± 5.6 to 52.6 ± 7.9 min (p < 0.05) with the pretreatment of EGCG.It can be speculated that the drug-drug interaction between EGCG and amlodipine might occur, which might have resulted from the metabolism inhibition of amlodipine by EGCG when they were co-administered.

Effects of triptolide on pharmacokinetics of amlodipine in rats by using LC–MS/MS

Context: Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in China clinics.Objective: This study investigated the effects of triptolide on the pharmacokinetics of amlodipine in male Sprague–Dawley rats.Materials and methods: The pharmacokinetics of amlodipine (1 mg/kg) with or without triptolide pre-treatment (2 mg/kg/day for seven days) were investigated using a sensitive and reliable LC–MS/MS method. Additionally, the inhibitory effects of triptolide on the metabolic stability of amlodipine were investigated using rat liver microsome incubation systems.Results: The results indicated that when the rats were pre-treated with triptolide, the Cmax of amlodipine increased from 13.78 ± 3.57 to 19.96 ± 4.56 ng/mL (p < 0.05), the Tmax increased from 4.04 ± 1.15 to 5.89 ± 1.64 h (p < 0.05), and the AUC0–t increased by approximately 104% (p < 0.05), which suggested that the pharmacokinetic behaviour of amlodipine was affected after oral co-administration of triptolide. Additionally, the metabolic half-life was prolonged from 22.5 ± 4.26 to 36.8 ± 6.37 min (p < 0.05) with the pre-treatment of triptolide.Conclusions: In conclusion, these results indicated that triptolide could affect the pharmacokinetics of amlodipine, possibly by inhibiting the metabolism of amlodipine in rat liver when they are co-administered.

Pharmacokinetic interaction between alcohol and two of the commonly prescribed anti-hypertensive drugs-amlodipine and nebivolol

Background: Alcoholism is one of the leading causes of secondary hypertension. Many a times in clinical setting, many hypertensive patients also happen to be alcoholics, either social/moderate drinkers or suffer from alcohol dependence. For these patients, cessation of alcohol consumption is advocated and counselled as part of diet and lifestyle modifications. However, compliance rates have been found to be variable. Therefore, these patients consume alcohol and also take anti-hypertensive medications on a day-to-day basis. This study was initiated to explore influence of alcohol on the pharmacokinetics of anti-hypertensive drugs – Amlodipine and Nebivolol.Methods: 24 human volunteers were recruited for the study after obtaining informed consent. 12 volunteers each for Amlodipine, Nebivolol and alcohol’s effect on the drugs respectively were evaluated. Two standard drinks of alcohol were administered in respective period as per randomization. Clinical confinement and blood sampling was carried out as per ethics committee approved protocol in accordance with good clinical practice principles.Plasma samples were analyzed using validated LC-MS/MS bio-analytical method, for quantification of Nebivolol and Amlodipine in lines with good laboratory practice principles. Pharmacokinetic and statistical analysis of results was evaluated using WinNonlin Version 5.3.Results: The pharmacokinetic parameters were evaluated statistically and ANOVA results suggest that despite changes in individual parameters, the bioavailability was comparable, as both Cmax and AUC0-inf were well within the range of 80-125%.Conclusions: It is clearly observed that there are variations in all pharmacokinetic parameters when the drug is administered with alcohol. However, the same are well within acceptable limits and bioavailability of the drugs is comparable when administered with alcohol. Hence, two standard drinks of alcohol have limited effect on the pharmacokinetics of Amlodipine and Nebivolol. Further studies are required to evaluate influence of higher and frequent doses of alcohol on pharmacokinetics of Amlodipine and Nebivolol.

Factors Influencing the Relationship Between the Dose of Amlodipine Required for Blood Pressure Control and Change in Blood Pressure in Hypertensive Cats.

BackgroundHypertension is a common problem in elderly cats. In most cats, systolic blood pressure (SBP) of <160 mmHg is achieved in response to amlodipine besylate at either 0.625 or 1.25 mg q24h. The individual cat factors determining dose requirement dose have not been explored.AimsTo determine whether individual cat factors influence the dose of amlodipine required to achieve adequate blood pressure control and to determine whether factors other than the prescribed dose of drug alter the achieved plasma amlodipine concentrations.MethodsFifty‐nine hypertensive cats that required 0.625 mg (A) and 41 cats that required 1.25 mg (B) amlodipine to reach a target SBP of <160 mmHg were identified, and plasma amlodipine concentrations were determined. Comparisons were made between groups, and multivariable linear regression models were performed to investigate predictors of antihypertensive response.ResultsCats that required a greater dose of amlodipine had significantly higher SBP at diagnosis of hypertension (A: (median [25th, 75th percentile]) 182 [175,192] mmHg; B: 207 [194,217] mmHg, P < .001), but comparable blood pressure was achieved after treatment. Plasma amlodipine concentrations were directly related to the dose of amlodipine administered. At diagnosis, cats in group B had significantly lower plasma potassium concentration (A: 4.1 [3.8,4.5]; B: 3.8 [3.6,4.2] mEq/L, P < .01). Weight did not differ between groups. The decrease in SBP was directly and independently associated with the SBP at diagnosis and the plasma amlodipine concentration.Conclusions and Clinical ImportanceCats with higher blood pressure at diagnosis might require a greater dose of amlodipine to control their blood pressure adequately. Differences in amlodipine pharmacokinetics between cats do not seem to play a role in the antihypertensive response.

Effect of Ginkgo Leaf Tablets on the Pharmacokinetics of Amlodipine in Rats.

Ginkgo leaf tablet (GLT) is an effective traditional Chinese multi-herbal formula, which is often combined with amlodipine for treating senile hypertension in clinic. The aim of this study was to study the pharmacokinetics of amlodipine after oral administration of amlodipine and GLT and to investigate the potential for pharmacokinetic herb-drug interactions between GLT and amlodipine in rats. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) analytical method was developed for quantification of amlodipine in rat plasma. The accuracy, precision, linearity, selectivity and recovery were all within an acceptable range. Male Sprague-Dawley rats were randomly assigned to two groups: amlodipine group and amlodipine+GLT group. Plasma concentrations of amlodipine were determined at the designated time points after oral administration by using the developed LC-MS/MS method, and the main pharmacokinetic parameters were calculated and compared. As ginkgolides A, ginkgolides B, bilobalide, quercetin and kaempferol were the main components of GLT, the effects of these ingredients in GLT on metabolism of amlodipine were further investigated in rat liver microsomes. The pharmacokinetic parameters, maximum plasma concentration (C max), time to reach C max (T max), area under the concentration-time curve (AUC), area under the first moment plasma concentration-time curve (AUMC) and elimination half-life (t 1/2), of amlodipine were significantly increased in amlodipine+GLT group, which suggested that GLT may influence the pharmacokinetic behavior after oral co-administration with amlodipine. Amlodipine is metabolized by cytochrome P450 (CYP) 3A4, so it was speculated that GLT may change the pharmacokinetic parameters of amlodipine through modulating the metabolism of CYP3A4 enzymes. When ginkgolides B, bilobalide, or quercetin and amlodipine were co-incubated in the rat liver microsomes, the metabolic rate of amlodipine was prolonged to 533.1, 216.1 and 407.6min, respectively, from 73.7min. These results suggested that these components in GLT inhibit the metabolism of amlodipine. So it can be speculated that the herb-drug interactions between GLT and amlodipine resulted from inhibiting the metabolism of amlodipine by GLT when they were co-administered.

Relationship Between Amlodipine Pharmacokinetics And Cyp3a Activity In Lactating Women With Pregnancy-Induced Hypertension

Relationship Between Amlodipine Pharmacokinetics And Cyp3a Activity In Lactating Women With Pregnancy-Induced Hypertension

ABCB1 Polymorphism and Gender Affect the Pharmacokinetics of Amlodipine in Chinese Patients with Essential Hypertension: A Population Analysis

The effects of genetic polymorphisms of ABCB1 C3435T, POR*28, CYP3A4*1G and CYP3A5*3 variants and gender relating to metabolism on the exposure and response of amlodipine in Chinese hypertensive patients were determined. Population pharmacokinetic analyses were performed on data which were collected prospectively from 60 Chinese patients with mild to moderate essential hypertension [age range 40-74 years, males (n = 31), females (n = 29)] receiving oral racemic amlodipine for 4 weeks. Blood pressure was evaluated at the end of weeks 0 and 4. Blood samples were collected in heparinized tubes at the following times: 0, 2, 6, and 24 h on about day 28 after administration of amlodipine. A one-compartment model with first-order elimination and absorption best described the amlodipine pharmacokinetic data. ABCB1 3435 genetic polymorphism and gender affect the amlodipine oral clearance (CL/F). CL/F (L/h) = 28.8 × (1 + GNDR)(-0.531) × (ABCB1 C3435T) where GNDR = 0 and 1 are for male and female, respectively. The CL/F value in a male patient with the ABCB1 3435CC or CT genotype is 28.8 L/h. Lower CL/F and higher exposure occurs in female subjects with the ABCB1 3435CC or CT genotype who have greater decreases in blood pressure after treatment with amlodipine. The results may help to improve the efficacy and tolerability of amlodipine in essential hypertensive patients.

The Influence of Food on the Pharmacokinetics of Amlodipine and Losartan after Single-Dose of its Compound Tablets in Healthy Chinese Subjects

We aim to identify the effects of food on the pharmacokinetics (PK) of amlodipine, losartan and losartan's active metabolite (EXP3174) after oral administration of the Compound Amlodipine Tablets with single dose in healthy Chinese subjects. 12 subjects took the compounds (10 mg/100 mg, amlodipine/losartan) at the conditions of a high-fat breakfast and an overnight fast with a washout period of 14 days. Plasma samples were obtained at scheduled time, and determined by HPLC-MS/MS for the concentrations of amlodipine and HPLC-MS for the concentrations of losartan and EXP3174, respectively. PK parameters were calculated using Software Drug and Statistics (Version 2.0). When tablets were co-administered with food, there was no significant difference of AUC for amlodipine and losartan, but the AUC of EXP3174 was reduced by 19.1%. Meanwhile, the Cmax of amlodipine, losartan and EXP3174 were reduced by 11.4%, 20.0% and 41.4%, and the Tmax of losartan and EXP3174 were 1.3 and 1.8 h longer, respectively. No significant difference was found at t1/2 following food intake. In conclusion, the Compound Amlodipine Tablets, are affected by food administration by reducing the AUC of EXP3174. It is thus suggested that the Compound Amlodipine Tablets should be administered 1 h before or 2 h after meal.