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Pharmacokinetics and metabolism of diltiazem in rats: comparing single vs repeated subcutaneous injections in vivo
Author(s) -
Yeung Pollen K. F.,
Alcos Angelita,
Tang Jinglan,
Tsui Ban
Publication year - 2007
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.568
Subject(s) - pharmacokinetics , diltiazem , in vivo , chemistry , pharmacology , metabolism , plasma concentration , metabolite , half life , endocrinology , medicine , biochemistry , calcium , biology , microbiology and biotechnology , organic chemistry
Abstract The objective of the study was to determine the effect of repeated administration on the pharmacokinetics and metabolism of diltiazem (DTZ) using an in vivo rat model. Male SD rats ( n = 6–10 per group) weighing 350–450 g were used. Each rat received either a single 20 mg/kg dose of DTZ by subcutaneous (s.c.) injection or 5 mg/kg s.c. twice daily for five doses. Plasma concentrations of DTZ and its major metabolites were determined by HPLC for up to 8 h. Compared with the single dose, repeated administration resulted in higher dose normalized plasma concentrations of DTZ ( AUC 26.4±14.2 vs 13.9±11.5 µg‐h/ml), longer apparent half‐life ( t 1/2 = 12.5±14.6 vs 3.7±1.4 h) and lower systemic clearance ( CL = 1.1±1.0 vs 2.9±2.7 l/h/kg). Higher dose normalized plasma concentrations, longer t max , but shorter apparent t 1/2 of the major metabolites were observed following the repeated administration. The results also suggest that possible binding of DTZ may occur at the site of injection when administered subcutaneously in the higher dose. Copyright © 2007 John Wiley & Sons, Ltd.