Benzylpenicillin kinetics in the ewe: influence of pregnancy and lactation

Benzylpenicillin kinetics were investigated in a breed of sheep adapted to life in barren areas. Important pharmacokinetic differences, dependent on reproductive status (control, pregnancy, lactation), were demonstrated. In control ewes, the steady state volume of distribution was 0.23 +/- 0.15 litre kg-1 and the plasma clearance was 12.4 +/- 3.19 ml kg-1 min-1. During pregnancy, these two parameters were not significantly modified. During lactation, the plasma clearance and volume of distribution were significantly higher than during the control period and pregnancy (27.4 +/- 3.22 ml kg-1 min-1 and 0.696 +/- 0.20 litre kg-1, respectively (P less than 0.01). In contrast the mean residence time (25.0 +/- 4.6 minutes) was similar to those of the control period (17.54 +/- 6.25 minutes) and pregnancy (23.18 +/- 5.94 minutes). These modifications in benzylpenicillin kinetics were explained in terms of fluid balance adjustments and renal function adaptation observed during pregnancy and lactation, and it is suggested that an appropriate dosage regimen for benzylpenicillin should take into account the physiological status of the animal.