Effect of Rifampicin on the Pharmacokinetics of Atenolol

Abstract

Also poorly metabolized drugs, including certain b-blocking agents, can be susceptible to drug interactions caused by transporter inhibitors and inducers. Thus, our aim was to investigate the effect of rifampicin on the pharmacokinetics of atenolol in healthy people. In a randomized cross-over study with two phases, nine healthy volunteers received a 5-day pretreatment with rifampicin (600 mg daily) or placebo. On day 6, a single 100 mg dose of atenolol was administered orally. The plasma concentrations of atenolol and its excretion into urine were measured up to 33 hr after dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the intake of atenolol and 2, 4, 6, and 10 hr later. During the rifampicin phase, the mean area under the plasma concentration-time curve (AUC 0-≤ ) of atenolol was decreased to 81% and renal clearance increased to 109% of the placebo phase values (PϽ0.05). Rifampicin pretreatment reduced, albeit not statistically significantly, also the peak plasma concentration (C max ), AUC 0-33 hr , and amount of atenolol excreted to 85% (PΩ0.139), 81% (PΩ0.053), and 86% (PΩ0.12) of the respective placebo phase values. The average heart rate and diastolic blood pressure were slightly higher during the rifampicin phase compared with the placebo phase (PϽ0.05). To conclude, although the inducing effect of rifampicin may not have been at its maximum by day 6, rifampicin has only a minor effect on the pharmacokinetics of atenolol evidenced by a slight reduction in its bioavailability.Atenolol is a cardioselective b-adrenoceptor-blocking agent used in the treatment of coronary heart disease, hypertension, and certain cardiac arrhythmias. The oral bioavailability is about 50%, mainly due to incomplete absorption (Dollery 1999). Metabolism only plays a negligible role in its elimination, and over 90% of the absorbed atenolol dose can be found as unchanged drug in urine. The mean elimination half-life of atenolol is approximately 6 hr (Wan et al. 1979).Also poorly metabolized compounds can be susceptible to pharmacokinetic drug-drug interactions. For instance, plasma concentrations of digoxin and celiprolol can be increased by concomitant itraconazole ingestion (Partanen et al. 1996;Lilja et al. 2003), and reduced by pretreatment with rifampicin (Greiner et al. 1999;Lilja et al. 2004). A previous study suggests that verapamil can increase plasma concentrations of atenolol (Keech et al. 1988). Furthermore, in a case report, blood pressure lowering effect of atenolol was found to be decreased during concomitant rifampicin (Goldberg et al. 2003).Rifampicin is a potent inducer of several cytochrome P450 enzymes and some transporters, and concomitant use of rifampicin with other drugs can reduce their absorption and increase their elimination (Greiner et al. 1999;Fromm et al. 2000;Niemi et al. 2003). The present study was conducted to investigate possible effects of rifampicin on the pharmacokinetics of atenolol in healthy persons.Author for corresponden...

Determination of celiprolol in human plasma using high performance liquid chromatography with fluorescence detection for clinical application

“…A delay in t max of celiprolol by apple juice was also observed. These results are consistent with previous studies regarding fruit juice and celiprolol interaction in humans [4,5].…”

“…Both of them are expressed in the intestine, and the transport function is inhibited by fruit juices including grapefruit, orange and apple juice [8,9]. These findings suggest that a reduced absorption of celiprolol in the intestine is the most likely mechanism for the fruit juice and celiprolol interaction [4,5]. However, clinical evidence for the fruit juice-drug interaction mediated by uptake transporters is limited.…”

“…In humans, itraconazole, a P-gp inhibitor, was reported to increase plasma celiprolol concentration without affecting the elimination half-life, indicating that the absorption of celiprolol was increased by inhibition of P-gp in the intestine [4]. On the other hand, fruit juices such as grapefruit juice and orange juice significantly reduce the bioavailability of celiprolol by 87% and 83%, respectively [4,5]. The remarkable reduction in the bioavailability of celiprolol by fruit juices can be considered to be clinically important.…”

Pharmacokinetic Drug Interactions of Antimicrobial Drugs: A Systematic Review on Oxazolidinones, Rifamycines, Macrolides, Fluoroquinolones, and Beta-Lactams

“…A placebo-controlled cross-over study in 9 healthy subjects found that RIF had a minor effect on the PK of atenolol, evidenced by a decrease of AUC 0-∞ to 81% and an increase of renal clearance to 109% [116]. RIF decreased talinolol AUC by 21% after intravenous and by 35% after oral administration, probably through increased P-gp mediated excretion [117].…”

Antioxidant properties of drugs used in Type 2 diabetes management: could they contribute to, confound or conceal effects of antioxidant therapy?

“…C max = 709 ± 221 ng/ ml AUC = 6120 ± 2171 ng.h/ml [41] isoprostanes as well as to increase concentrations of an erythrocyte antioxidant enzyme, superoxide dismutase (SOD) [59,62,66,69,81,87,93,95]. Although both in vitro and in vivo studies provide evidence of the antioxidant properties of statins, conflict exists with regard to the effect of statins on plasma tocopherols (vitamin E).…”