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, CLNR) 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 CLNRs 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 (CLint), free fraction in plasma (fp) and hepatic blood flow rate (QH) depending on the hepatic excretion ratios of drugs. In general, changes in the CLNRs 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.

Pharmacokinetics of drugs in mutant Nagase analbuminemic rats and responses to select diuretics

“…In male SD rats, azosemide, a loop diuretic, is metabolized via hepatic CYP1A1/2 [21] but not CYP2E1. [51] After i.v. administration of azosemide to male NARs, its plasma CLNR (which could represent its metabolic clearance [50] ) was more rapid (by 307%) than that in control rats [6] (Table 3).…”