Tertatolol in chronic renal failure. A pharmacokinetic study

Pharmacokinetics of tertatolol were investigated in 22 hypertensive patients (12 men and 10 women; mean age +/- SD: 52.6 +/- 12.3 years) with chronic renal failure defined by a mean creatinine clearance (Clcr) of 24.6 +/- 15.9 mL/min/1.73 m2 (range: 6.2 to 68.7). A daily single dose of 5 mg tertatolol was administered orally for 4 weeks, except in the 72 h following the first administration. Plasma samples and urine collections were carried out over 72 h after the first (D0) and the last dose (D27). After the first administration, tertatolol was rapidly absorbed (time to peak concentration: 1.2 +/- 0.7 h) and peak concentration was 160 +/- 80 ng/mL. Plasma concentrations decreased following a biphasic curve, with two half-lives of 2.5 +/- 1.1 and 17.0 +/- 8.5 h, respectively. These parameters were not modified by repeated administration of tertatolol and did not significantly correlate with Clcr either at D0 or at D27. Plasma levels were stable along the study with similar areas under plasma curves following the first and the last dose (P = NS). In addition, plasma levels extrapolated from first dose data did not significantly differ from those observed during repeated dosage. Plasma levels of the 4-OH metabolite which possesses a beta-blocking activity were low, inconstantly detectable, not related to the degree of renal impairment, and no accumulation occurred after chronic dosage. Renal excretion of tertatolol and 4-OH tertatolol was significantly increased by repeated administration (P less than .01) and correlated well with Clcr either at D0 or at D27. Four week treatment was well tolerated and significantly improved Clcr (+6.5%, P less than .02). In conclusion, tertatolol was well tolerated and did not accumulate in patients with renal failure of various degrees. The usual daily single dose of 5 mg may be kept unchanged whatever the degree of renal impairment.