rifampin and Essential-Hypertension

Esaxerenone is a novel, non-steroidal mineralocorticoid receptor (MR) blocker with improved selectivity and affinity for MR. The objectives of this study were to model the population pharmacokinetics of esaxerenone in a diverse population and to evaluate the effect of covariates on pharmacokinetics parameters.. A total of 8263 plasma esaxerenone concentrations from 166 healthy volunteers, 1097 hypertensive patients and 360 patients with diabetic nephropathy were pooled. A three-compartment model with sequential zero- and first-order absorption was used to describe the time-courses of plasma esaxerenone following single and multiple doses once daily for up to 12 weeks. Covariate effects were estimated using the full covariate modeling approach. Clinical relevance of covariates was ascertained using tornado plots.. Esaxerenone was estimated to have high bioavailability (85.3%), low clearance (3.28 L/h) and relatively large distribution volume at steady state (94.8 L). Body weight (-26 to +36%) and coadministration of itraconazole (+64%) or rifampicin (-68%) were associated with a greater influence on esaxerenone exposure.. The most influential covariates on esaxerenone exposure were coadministrations of itraconazole and rifampicin, followed by body weight. The clinical relevance of effects of renal impairment, mild to moderate hepatic impairment, and age is limited.

Topics: Body Weight; Diabetes Mellitus; Diabetic Nephropathies; Essential Hypertension; Healthy Volunteers; Humans; Itraconazole; Receptors, Mineralocorticoid; Rifampin

Dihydropyridine calcium-channel blockers are a known substrate for the cytochrome P450 isoform 3A4. Rifampicin, an antitubercular agent, is one of the most potent inducers of hepatic and intestinal CYP3A4 thus increasing dihydropyridine metabolism. We report a case of a 67-year-old hypertensive female treated with a four-drug antihypertensive regimen including a dihydropyridine (nicardipine 50 mg bid), who was admitted for septic arthritis of the knee requiring antibiotic treatment with teicoplanin 400 mg od and rifampicin 600 mg bid. Six days after rifampicin initiation, she presented with Posterior Reversible Encephalopathy Syndrome due to uncontrolled hypertension. We hypothesized that disequilibrium of previously controlled hypertension was partially due to nicardipine ineffectiveness. Plasma nicardipine concentration was assessed through high-performance liquid chromatography 5 hours after coadministration of the two drugs and proved undetectable.

Topics: Aged; Antibiotics, Antitubercular; Antihypertensive Agents; Calcium Channel Blockers; Drug Interactions; Essential Hypertension; Female; Humans; Nicardipine; Rifampin