Pharmacokinetics of drugs in spontaneously or secondary hypertensive rats

Abstract

1. Spontaneously hypertensive rats (SHRs) and deoxycorticosterone acetate–salt-induced hypertensive rats (DOCA–salt rats) have been developed as animal models for human essential (idiopathic or primary) and secondary hypertensions, respectively.

2. In order to identify pharmacokinetic changes (mainly non-renal clearance, CL_NR) in 16-week-old SHRs due to hereditary characteristics and/or neither the hypertensive state itself, we reviewed the pharmacokinetics of drugs in 6- (blood pressure within a normotensive range) and 16-week-old SHRs and 16-week-old DOCA–salt rats compared with respective control rats.

3. We reviewed changes in CL_NRs of drugs which are primarily metabolized via hepatic microsomal cytochrome P 450 enzymes (CYPs) based mainly on data from hypertensive rats, and present the data in terms of changes in in vitro hepatic intrinsic clearance (CL_int), free fraction in plasma (f_p) and hepatic blood flow rate (Q_H) depending on the hepatic excretion ratios of drugs. In general, changes in the CL_NRs of drugs in this category were well-explained by the above-described factors.

4. We also reviewed and discussed the mechanism of urinary excretion of drugs (i.e. glomerular filtration and active renal secretion or reabsorption) in hypertensive rats.

• Hepatic cytochrome P 450 (CYPs)
• pharmacokinetics
• spontaneously or secondary hypertensive rats