Drug-drug interaction between irbesartan and hydrochlorothiazide in renal hypertensive rats: A case study of dose optimization

Abstract

Abstract: AIM: To quantitatively study the dose optimization of drug-drug interaction of irbesartan and hydrochlorothiazide in renal hypertensive rats using weighted modification model and nonlinear mixed effect model.METHODS: Renal hypertensive rats were randomly divided into six groups with different dose combination according to the experimental design of weighted modification method. The rates of change of systolic and diastolic blood pressures were measured as pharmacodynamic indices. Original and population weighted modification methods were comprehensively used to analyze the experimental data and evaluate the drug-drug interaction and dose optimization of irbesartan/hydrochlorothiazide in rats. The results and characteristics of original and population weighted modification methods were compared.RESULTS:The weighted modification models were built successfully. The optimal combination proportion between these two drugs was 10∶1 (irbesartan/hydrochlorothiazide) and the nature of interaction was synergism. The role of irbesartan is more important than that of hydrochlorothiazide when used combinedly. The basic research conclusions of original and population weighted modification methods were the same. However, population weighted modification method can provide more accurate parameters such as weighted index and useful information of inter- and intra-individual variabilities.CONCLUSION: The weighted modification methods can be used to quantitatively evaluate the drug-drug interaction and dose optimization of irbesartan/hydrochlorothiazide in rats.

Key words: Irbesartan, Hydrochlorothiazide, Weighted modification method, Nonlinear mixed effect model, Dose optimization

CLC Number:

R544.1

HUANG Xiao-hui, WANG Qin, WANG Kun, HUANG Ji-han, QIU Fu-rong, TANG Hai-qin, LI Jun. Drug-drug interaction between irbesartan and hydrochlorothiazide in renal hypertensive rats: A case study of dose optimization[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(5): 521-528.

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