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Betaxolol kinetics in hypertensive children with normal and abnormal renal function
Insights
Betaxolol, a beta 1-selective blocker, shows predictable pharmacokinetics in children with renal failure. Renal impairment doubles the half-life (t1/2) in severe cases, but it maintains an antihypertensive effect.
Area of Science:
- Pharmacology
- Pediatrics
- Nephrology
Background:
- Betaxolol is a beta 1-selective adrenergic receptor antagonist.
- Children with chronic renal hypertension and varying degrees of renal failure require careful medication management.
- Understanding drug disposition in pediatric patients with renal impairment is crucial for effective treatment.
Purpose of the Study:
- To evaluate the pharmacokinetic and clinical profile of betaxolol in children aged 5 to 13 years with chronic renal hypertension and renal failure.
- To assess the impact of renal failure on betaxolol's disposition and its antihypertensive efficacy.
Main Methods:
- Ten pediatric patients (5-13 years) with chronic renal hypertension and renal failure received an intravenous dose followed by oral doses of betaxolol.
- Pharmacokinetic parameters including half-life (t1/2), total clearance, and volume of distribution were measured.
- Clinical response, including blood pressure reduction, was monitored throughout the study.
Main Results:
- Betaxolol exhibited 80% to 90% bioavailability with a half-life of 16 to 20 hours.
- Total clearance was 0.30 L/kg/hr and volume of distribution was 8.2 L/kg.
- Half-life (t1/2) correlated linearly with serum creatinine levels, doubling in severe renal failure cases.
- Betaxolol demonstrated an antihypertensive effect, maintaining previous responses and reducing blood pressure in newly treated patients.
Conclusions:
- Betaxolol disposition in children with renal failure is comparable to young healthy adults, suggesting significant non-renal clearance.
- Renal failure prolongs betaxolol's half-life, particularly in severe cases, similar to adult patients.
- Betaxolol is effective in managing hypertension in pediatric patients with renal failure.
Abstract:
The kinetic and clinical profile of betaxolol--a beta 1-selective blocker with 80% to 90% bioavailability and a 16 to 20 hr t1/2--were studied in ten children aged 5 to 13 yr with chronic renal hypertension and mild to severe renal failure. An IV dose of 20 mg of betaxolol per 1.73 m2 body surface area (BSA) was followed by six daily oral doses. Six patients were maintained on combination therapy and four on betaxolol alone; two of these were newly treated. After the intravenous dose, t1/2 (mean +/- SE) was 19.9 +/- 1.7 hr, total clearance 0.30 +/- 0.03 l/kg/hr, and volume of distribution 8.2 +/- 0.7 l/kg. Clearance adjusted for BSA was 7.9 +/- 0.6 l/hr. The t1/2 correlated linearly to serum creatinine levels. After the last dose, peak concentration was 97.4 +/- 7.6 ng/ml, and t1/2 19.4 +/- 2.7 hr. Betaxolol 24-hr blood levels were twice as high as after the first dose. Blood pressure was reduced in two newly treated patients and two patients on combination therapy; previous responses were maintained in the others. The maximum effect was reached after the first dose and was maintained throughout the study week. Our results indicate that betaxolol disposition in children aged 5 to 13 yr with different degrees of renal failure is of the same order as that in young healthy adults, implying that there may be a higher rate of non-renal clearance. Renal failure-induced modification led to a doubling of the t1/2 in the most severe cases, again as in adult renal patients. There is an antihypertensive effect.