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PII‐66
Author(s) -
Yeung P. K.,
Alcos A.,
Tang J.,
Tsui B. C.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.191
Subject(s) - diltiazem , in vivo , hemodynamics , subcutaneous injection , medicine , anesthesia , pharmacology , biology , calcium , microbiology and biotechnology
AIMS To compare the pharmacokinetics and hemodynamic effect of diltiazem (DTZ) following single and repeated subcutaneous injection using an in vivo rat model. METHODS Male SD rats (n = 5 – 6 per group) weighing between 350 – 450g were used. Each rat received either a single 20 mg/kg dose of DTZ (Biovail Corp, Mississauga, Ont. Canada) by s.c. injection or 5 mg/kg s.c. bid for 5 doses. Plasma concentrations of DTZ and its major metabolites were determined by a previously published HPLC for up to 6h. In addition, hemodynamic measurements were recorded continuously for each animal during the experiment. RESULTS DTZ decreased SBP from 138 +/− 9 to 124 +/− 8 mmHg (10%) following the single dose and from 126 +/− 17 to 104 +/− 10 mm Hg (17%) following the 5 th and last dose. The effects on DBP were also greater following the multiple doses (33% vs 26%), and the effects were also more sustainable after the repeated dosing. Plasma concentrations of DTZ were considerably higher after the single 20 mg/kg dose (AUC 8185 vs 3505 ng‐h/mL), although the half‐lives were longer at steady‐state (6 vs 2h). There were no apparent differences in the metabolite profiles. CONCLUSION Hemodynamic effects of DTZ were both qualitatively and quantitatively different between the single dose and steady‐state dosing. The reason is not completely clear although it may be related to greater tissue distribution of DTZ following repeated administration. (Supported in part by a grant‐in‐aid from CIHR/NSHRF/PEF Regional Partnership Program.) Clinical Pharmacology & Therapeutics (2005) 79 , P53–P53; doi: 10.1016/j.clpt.2005.12.191