The pharmacokinetics of mecillinam and pivmecillinam in pregnant and non-pregnant women

Abstract

1. The pharmacokinetics of parenteral mecillinam (n = 27) and oral pivmecillinam (n = 12) were studied in pregnant (n = 27) and non-pregnant (n = 12) subjects. 2. In early pregnancy (9-14 weeks of gestation) the mean peak plasma drug concentration (Cmax = 19 +/- 9 micrograms ml-1) after an intravenous injection of 200 mg mecillinam was significantly lower (P less than 0.05) and the volume of distribution (V = 49 +/- 20.1) significantly larger (P less than 0.05) than in non-pregnant subjects (Cmax = 35 +/- 18 micrograms ml-1, V = 29 +/- 12.1). In late pregnancy (39-40 weeks of gestation) the plasma mean peak concentration (Cmax = (29 +/- 14 micrograms ml-1) after parenteral administration of 200 mg mecillinam was slightly lower and the volume of distribution (V = 65 +/- 29.1, V = 0.9 +/- 0.4 l kg-1) significantly larger than that in non-pregnant subjects (V = 0.4 +/- 0.3 l kg-1). Also after oral administration of 200 mg pivmecillinam, equimolar to 136.5 mg mecillinam, the mean peak plasma concentration in pregnant subjects (Cmax = 1.8 +/- 1.2 micrograms ml-1) was slightly lower than that in non-pregnant subjects (Cmax = 1.7 +/- 1.2 micrograms ml-1). 3. The mean half-life of elimination after parenteral administration of mecillinam was significantly longer during both early (t1/2,Z = 133 +/- 38 min, P less than 0.05) and late pregnancy (t1/2,Z = 107 +/- 41 min, P less than 0.05) as compared with the non-pregnant state (t1/2,Z = 75 +/- 21 min).(ABSTRACT TRUNCATED AT 250 WORDS)