Clinical pharmacokinetics of methylergometrine (methylergonovine).

Pharmacokinetic studies carried out on methylergometrine (methylergonovine) by a radioimmunoassay are reviewed. After intravenous injection the half-life of the distribution phase was only 1-3 min, explaining the fast and strong oxytocic response in puerperal mothers. The fast tissue uptake was also obtained in the rabbit uterus in situ with a steep dose-response curve. The rate of gastrointestinal absorption appeared to be slower in patients during puerperium (Tmax 3 h) in comparison with healthy male volunteers (Tmax 0.5 h). The bioavailability after administration was about 60%. After intramuscular injection the rate of absorption was rapid (Tmax 0.5 h). The short half-life of the elimination phase (about 0.5-2 h), low apparent volume of distribution (about that of extracellular water of the body), and the relatively high total plasma clearance value (about 120-240 ml/min) were direct evidence of the rapid elimination of the drug from the body. After repeated oral administrations no accumulation was found. Only about 3% of the single oral dose was excreted into urine, indicating hepatic metabolism and elimination. Although methylergometrine had a good penetration into breast milk in dogs, in postpartum women the mild concentrations were hardly measurable and clinically nonsignificant. Apparently there is no correlation between the plasma level and clinical effect of methylergometrine.