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>Clearance Prediction and Drug Dosage in PregnancyA Clinical Study on Metildigoxin, and Application to other Drugs with Predominant Renal Elimination
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Clearance Prediction and Drug Dosage in PregnancyA Clinical Study on Metildigoxin, and Application to other Drugs with Predominant Renal Elimination
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机译：Clearance Prediction and Drug Dosage in PregnancyA Clinical Study on Metildigoxin, and Application to other Drugs with Predominant Renal Elimination
The clearance of drugs with predominantly renal elimination is increased in pregnancy. The approach given in this paper for clearance prediction is based on the concept of parallel renal and nonrenal elimination, and on the assumption that clearance is increased as a result of a pregnancy-induced increase in the renal component, while the nonrenal component is assumed to remain essentially constant. The expected elimination capacity is then defined as the ratio of pregnant to normal nonpregnant clearances (QPrequals; clsol;CL), and can be calculated by the following equation: QPrequals; QNRplus; (1-QNR) middot; 1.5, where QNRis the normal, nonrenal elimination fraction. The expected elimination capacity provides a first estimate for the dosage adjustment, performed either by increasing the maintenance dose, D: d equals; D middot; QPr, where d is the adjusted maintenance dose, or by reducing the dosage interval, T: t equals; Tsol;QPr, where t is the adjusted dosage interval.We tested this approach for clearance prediction with pregnant and nonpregnant clearance data of metildigoxin, ampicillin and cefuroxime. Data on metildigoxin were obtained from 8 patients treated for maternal or fetal indications according to published recommendations. The observed clearance was significantly higher than the normal nonpregnant value (183vs140 mlsol;min), and closely matched the predicted value (189 mlsol;min). Clearance predictions for ampicillin and cefuroxime were performed using published data, and again close agreement was found between predicted and published clearance values.
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