Pharmacokinetics and pharmacodynamics of heparin during hemodialysis: interpatient and intrapatient variability

Heparin pharmacokinetics and pharmacodynamics were studied in 17 patients undergoing hemodialysis, once a week for 4 weeks in order to evaluate intrapatient variability over time. A single bolus injection of heparin was administered directly into the circulation immediately prior to the start of hemodialysis in doses ranging from 3000 to 12,000 U. Blood samples were obtained to determine activated coagulation times (ACT) and heparin concentrations (HC). Combined zero- and first-order elimination was seen in each of the 4 weeks. The half-life of heparin decreased from beginning to end of hemodialysis during each week, with the percentage of decrease from the start of dialysis ranging from 70-74%, indicating concentration-dependent elimination. Since the zero-order component did not appear to be clinically significant, first-order elimination was assumed. A linear decline in ACT over the time of the dialysis period was also seen during each week. A profile of ACT versus HC was generated for each patient as well as for the mean data to assess the relationship of HC to response. An excellent correlation was found for both individual patient data and mean data. In the third week the patients were randomized to receive standard treatment or an individualized dose. They were then crossed over to the opposite group in the fourth week to see if this relationship between ACT and HC would be useful in predicting heparin dose. These profiles were used to individualize the dose during either the third or fourth week of the study. No significant differences were noted between actual and predicted ACT. A significant degree of interpatient variability was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)