Lack of effect of isradipine on cyclosporin pharmacokinetics.
The influence of isradipine as a long acting form (IcazR 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 SandimmuneR-RIA kit (specific and non-specific monoclonal antibodies). Area under the blood concentration-time curve (AUC), the maximum blood concentration (Cmax) and the time to reach Cmax (Tmax) 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) microgram.1(-1).h for the specific and 20,905 +/- 8,317 vs 19,327 +/- 5,758 microgram.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.(ABSTRACT TRUNCATED AT 250 WORDS)
Vernillet
L
L
Pharmaceutical Research Centre, Sandoz, SA, Rueil-Malmaison, France.
Bourbigot
B
B
Codet
J P
JP
Le Saux
L
L
Moal
M C
MC
Morin
J F
JF
D000328:Adult; D003524:Cyclosporins / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D017275:Isradipine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
D003524:Cyclosporins; D017275:Isradipine