Aminophylline alters pharmacokinetics of carbamazepine but not that of sodium valproate--a single dose pharmacokinetic study in human volunteers.

ABSTRACT

Pharmacokinetic interaction of aminophylline with single dose sodium valproate (400 mg) and carbamazepine (200 mg) was evaluated in normal healthy volunteers using a cross over design. Neither the serum concentrations nor the pharmacokinetic parameters of sodium valproate (SV) were altered by the coadministration of aminophylline (AMP). In contrast AMP significantly decreased the plasma concentrations of carbamazepine (CBZ). The Cmax of CBZ was significantly lowered from 1.73 +/- 0.18 to 0.94 +/- 0.08 microgram/ml and the AUC o-t was significantly decreased from 76.19 +/- 6.20 to 52.66 +/- 1.84 micrograms/h/ml (P < 0.05). The pharmacokinetic parameters of CBZ that were altered in the presence of AMP were the Tmax and t1/2 which was prolonged about threefold from 5.60 +/- 1.60 to 16.80 +/- 7.94 h and 44.88 +/- 4.50 to 125.07 +/- 29.09 h, respectively. The Vd was marginally increased from 2.19 +/- 0.13 to 3.85 +/- 0.57 L/kg and the Cl was decreased from 34.07 +/- 3.78 to 25.26 +/- 5.15 mL/min. None of these alterations are statistically significant. Bioavailability of CBZ was reduced by 29% in the presence of AMP, while that of SV was increased by about 8%. Results are of clinical significance because simultaneous administration of CBZ and AMP may reduce the efficacy of CBZ in epileptic patients.