In:
The Journal of Clinical Pharmacology, Wiley, Vol. 35, No. 3 ( 1995-03), p. 268-274
Abstract:
The negative inotropic and chronotropic effects of β‐blocker therapy have been reported to reduce morbidity and mortality in patients with Marfan syndrome; however, little is known about the pharmacokinetics of atenolol after oral administration of multiple doses to patients with the Marfan syndrome. We studied the pharmacokinetics of atenolol in 13 such patients aged 18.7 ± 2.9 years who were receiving 1.78 ± 0.58 mg/kg/day (70.1 ± 20.3 mg/m 2 /day) of atenolol for 6 weeks or longer. Mean ± SD percentage change in baseline heart rate after the administration of atenolol was −18.03 ± 16.59% and mean ± SD percentage change in exercise heart rate after atenolol was −33.22 ± 14.75% ( P 〈 .01). Six to 8 atenolol serum concentrations were collected in each patient during a 12‐hour dosing interval and were determined by high‐performance liquid chromatography with ultraviolet detection. Serum atenolol concentrations at 0 (123 ± 70 μg/L) and 12 (116 ± 66 μg/L) hours were within 20% of each other and were thus assumed to be at steady‐state. A one‐compartment, steady‐state pharmacokinetic model with first‐order absorption and elimination was fitted to the concentration‐time data for each patient using nonlinear regression. Maximal concentration was 343 ± 120 μg/L, and the mean half‐life was 4.72 hours. Pharmacokinetic parameters were as follows: Absorption rate constant (k a 〉 ) was 1.03 ± 1.34 hr −1 ; elimination rate constant (k) was 0.230 ± 0.220 hr −1 ; the ratio of bioavailability to volume of distribution (f/V d ) was 0.00612 ± 0.00214 L −1 ; area under the concentration‐time curve at steady‐state (AUC) was 2919 ± 1175 μghr/L; and the time at which the highest concentration occurred (t max ) was 1.87 ± 0.16 hours. Additionally, the dose‐normalized AUC ranged from 20.9 to 57.8 μg hr/L. Although there was considerable variability in the pharmacokinetics of atenolol in patients with the Marfan syndrome, the variability was similar to that reported in patients without Marfan syndrome .
Type of Medium:
Online Resource
ISSN:
0091-2700
,
1552-4604
DOI:
10.1002/jcph.1995.35.issue-3
DOI:
10.1002/j.1552-4604.1995.tb04057.x
Language:
English
Publisher:
Wiley
Publication Date:
1995
detail.hit.zdb_id:
2010253-7
SSG:
15,3
