Search Results - (Author, Cooperation:S. Fujiyama)

2012-06-16

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

1432-1041

Key words Lansoprazole ; CYP2C19; genotype ; hydroxy lation ; polymorphism ; pharmacokinetics

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Abstract Objective: 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. Methods: 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. Results: 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. Conclusion: The hydroxylation of lansoprazole to 5-hydroxylansoprazole was apparently impaired in the subjects with the genetic defects of CYP2C19 (m1/m1 or m1/m2).

Electronic Resource

1432-1041

famotidine ; H2-receptor antagonist ; renal insufficiency ; old age pharmacokinetics

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary The pharmacokinetics of the H2-receptor antagonist famotidine, after oral administration of a 20 mg tablet, has been studied in 10 elderly patients with normal renal function (CLCR≧59 ml·min−1, Mean=80 ml·min−1), 5 elderly patients with renal insufficiency (CLCR≦38 ml·min−1, Mean=15 ml·min−1), and 6 healthy young volunteers. Elimination half-life in the elderly patients with renal insufficiency was significantly prolonged compared to the elderly patients with normal renal function and the young volunteers. The correlation coefficient between creatinine clearance and the elimination rate constant of famotidine was 0.672. Mean urinary recovery of unchanged drug up to 24 h in the young volunteers was 44%. The mean renal clearance of famotidine in the young volunteers (270 ml·min−1) was substantially greater than the creatinine clearance, 128 ml·min−1, which suggests the possibility of tubular secretion of famotidine.

Electronic Resource

1432-1041

famotidine ; anuric patients ; haemodialysis ; H2-receptor antagonist ; pharmacokinetics

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Summary The effect of haemodialysis on the pharmacokinetics of oral famotidine has been studied in five elderly anuric patients. Famotidine 20 mg was administered in a cross-over design to patients on and not on haemodialysis. The elimination rate constant of haemodialysis (k) was 4.6-fold larger than the systemic elimination rate constant (ke). Although the mean maximum serum concentration of famotidine during haemodialysis (141.5 ng·ml−1) was not significantly lower than that without haemodialysis (195.6 ng·ml−1), the AUC up to 5 h during haemodialysis was significantly decreased to 58.1% of the value without it. The data suggest that famotidine is dialysable by haemodialysis.

Electronic Resource