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Lack of effect of isradipine on cyclosporin pharmacokinetics
Author(s) -
Vernillet L.,
Bourbigot B.,
Codet JP,
Saux L.,
Moal MC,
Morin JF
Publication year - 1992
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.1992.tb00132.x
Subject(s) - cmax , pharmacokinetics , isradipine , medicine , microgram , radioimmunoassay , pharmacology , morning , blood pressure , supine position , area under the curve , chemistry , antagonist , in vitro , biochemistry , receptor
Summary— The influence of isradipine as a long acting form (Icaz R LP 5 mg) on cyclosporin pharmacokinetics was studied in six hypertensive renal transplant patients (mean age 37 yrs; mean body weight 62 kg). These patients received a mean daily cyclosporin dose of 307 mg in two equal intakes. Isradipine was orally administered once a day at a dose of 5 mg before the morning cyclosporin intake. Cyclosporin kinetics was assessed over a 0–12‐h period, the day before (D‐1) and 13 days (D+13) after isradipine treatment. Whole blood concentrations of cyclosporin were determined by radioimmunoassay (RIA) using the Sandimmune R ‐RIA kit (specific and non‐specific monoclonal antibodies). Area under the blood concentration‐time curve (AUC), the maximum blood concentration (C max ) and the time to reach C max (T max ) on D‐1 and D+13 were not significantly different whatever the specificity of the RIA method. For example, the mean AUC ± sd values were 5 247 ± 2 255 (D‐1) vs 5 317 ± 1 675 (D+13) μg·1 −1 ·h for the specific and 20 905 ± 8 317 vs 19 327 ± 5 758 μg·1 −1 ·h for the non‐specific determinations. Therefore, the pharmacokinetics of cyclosporin is not influenced by co‐administration of isradipine at a therapeutic dosage. Moreover, the clinical results show that isradipine treatment was effective after 13 days administration (mean systolic blood pressure 132 vs 158 mm Hg, P < 0.05 and mean diastolic blood pressure 77 vs 93 mm Hg, P < 0.05 in supine position), and well tolerated throughout the study. Thus, the use of isradipine in its long acting form allows cyclosporin to be administered to transplant patients with no special adjustment of the dosage, unlike most other calcium channel blocking agents.