Pharmacokinetics Of Lansoprazole Research Articles

Oral pharmacokinetics of lansoprazole (L) after single and multiple doses as intact capsule and as simplified lansoprazole suspension (SLS)

Oral pharmacokinetics of lansoprazole (L) after single and multiple doses as intact capsule and as simplified lansoprazole suspension (SLS)

Genetic polymorphism of CYP2C19 and lansoprazole pharmacokinetics in Japanese subjects.

We investigated whether interindividual differences in the pharmacokinetic disposition of lansoprazole are attributed to the genetic polymorphism of CYP2C19 which occurred by two mutations. CYP2C19m1 and CYP2C19m2, in 20 Japanese subjects. Polymerase chain reaction (PCR) restriction fragment length polymorphism procedures were used to detect the CYP2C19m1 mutation in exon 5 and the CYP2C19m2 mutation in exon 4 using SmaI and BamHI, respectively. Ten subjects were homozygous (wt/wt subjects) for the wt allele in both exon 5 and exon 4, four subjects were heterozygous (wt/m1) for the CYP2C19m1 mutation, and two subjects were heterozygous (wt/m2) for the CYP2C19m2. The remaining four subjects had both mutated alleles in CYP2C19 genes, i.e., two were homozygous (m1/m1) for the defect in exon 5 and two were heterozygous (m1/m2) for the two defects in exons 5 and 4. The subjects in group 1 (wt/wt, wt/m1 and wt/m2) were the extensive metabolizers (EMs) for 5-hydroxylation of lansoprazole and were in the range of hydroxylation indexes from 3.83 to 19.8, whereas the subjects in group 2 (m1/m1 and m1/m2) were the poor metabolizers (PMs) and the indexes were in the range of 38.5 to 47.6. In group 2, AUC, t1/2 and CL/f of lansoprazole were significantly greater, longer, and lower, respectively, than those in group 1.

Lansoprazole pharmacokinetics in subjects with various degrees of kidney function.

The pharmacokinetics of lansoprazole, a new benzimidazole proton pump inhibitor, was evaluated after multiple-dose oral administration to 20 subjects with various degrees of kidney function. Multiple blood samples were obtained after doses 1 and 7 of the once-daily seven-dose regimen, and plasma concentrations of lansoprazole and five metabolites were quantitated with use of HPLC. The free fraction of lansoprazole increased as kidney function declined. A significant, although weak, relationship existed between creatinine clearance (CLCR) and area under the plasma concentration versus time curve (AUC) and terminal disposition half-life (t1/2), calculated with total concentration data. Those individuals with lower CLCR values also had lower total AUC and t1/2 values. However, there was no statistically significant relationship between CLCR and peak plasma concentration or AUC, calculated with unbound concentration data. No adjustment of lansoprazole dose is recommended on the basis of impaired kidney function.

健常人におけるＬａｎｓｏｐｒａｚｏｌｅの立体選択的体内動態

健常人におけるＬａｎｓｏｐｒａｚｏｌｅの立体選択的体内動態

Clinical Pharmacokinetics of Lansoprazole

Lansoprazole, a benzimidazole derivative with antisecretory and antiulcer activities, inhibits the acid pump activity at the final stage of the enzyme process and therefore reduces the acid secretion of parietal cells. Lansoprazole is converted to active metabolites in the acid environment of these cells. It is rapidly absorbed from a gastric acid-resistant formulation and is approximately 97% bound in human plasma. Single dose pharmacokinetics of lansoprazole appear to be linear over the range from 15 to 60mg. Food and time of dose influence absorption after single doses, but do not modify the antisecretory effect of multiple doses. Lansoprazole is extensively metabolised following oral administration into sulphone and 5-hydroxylated metabolites by the cytochrome P450 enzymes CYP3A4 and CYP2C18. Two other metabolites have been identified in plasma: sulphide and hydroxylated sulphone. Mean plasma elimination half-life (t1/2) is between 1.3 and 2.1 hours in healthy volunteers. 15 to 23% of the total dose is found in urine as free and conjugated hydroxylated metabolites, while unchanged lansoprazole is not detected. The pharmacokinetic profile of the drug is not modified by multiple administration. In healthy elderly volunteers, area under the plasma concentration-time curve (AUC) and t1/2 are significantly greater after single administration occurs to the same extent as in young volunteers. Renal failure has no influence on the pharmacokinetics of lansoprazole, but severe hepatic failure causes a significant decrease in clearance and an increase in the AUC and t1/2 of lansoprazole. This is accompanied by modifications in the AUC of metabolites, but severe hepatic failure has minimal effect on accumulation of the drug after multiple administration. The pharmacokinetics of lansoprazole in patients with acid-related disorders do not differ from those in healthy volunteers. Studies of interactions of lansoprazole with warfarin, prednisone, theophylline, phenazone (antipyrine), diazepam, phenytoin and oral contraceptives suggest minimal risk of any clinically significant interaction.

Ｌａｎｓｏｐｒａｚｏｌｅの体内動態に及ぼす酸化的代謝の影響

Ｌａｎｓｏｐｒａｚｏｌｅの体内動態に及ぼす酸化的代謝の影響

Single and multiple dose pharmacokinetics of lansoprazole in elderly subjects.

Plasma concentrations of lansoprazole and of its sulphone, sulphide and 5-hydroxylated metabolites were determined after oral administration of a single 30 mg dose and after 7 days of treatment with a daily 30 mg dose in 12 elderly subjects (mean age 83 years). Results after a single dose were compared with those from a historical control group of 18 young subjects (mean age 23 years). Mean values of AUC after single dose were 2668 ng ml(-1) h in the young subjects and 5216 ng ml(-1) h in the elderly (P < 0.05). Mean t 1/2z values in young and elderly subjects were 1.4 h and 2.9 h, respectively (P < 0.001). Plasma concentrations of the metabolites were similar in both groups. However, the hydroxylated metabolite of the sulphone was detected only in elderly subjects. Steady state plasma concentrations of lansoprazole were reached after 3 days of dosing with lansoprazole. The accumulation ratio was 1.31 in the elderly subjects.