Abstract
1. The pharmacokinetics of single intravenous doses of antipyrine were determined in 96 volunteers using multiple (12 or more) plasma antipyrine concentrations measured by high-pressure liquid chromatography during 24-48 h after dosage. These kinetic estimates were compared with those based on: A, the 4 h and 12 h points only; B, the 4 h through 12 h points; C, the 8 h and 24 h points only. 2. Mean clearance values for the complete study (48.0 ml min-1) were nearly identical to abbreviated approaches A, B, and C (49.1, 49.3, and 46.4 ml min-1), and were highly correlated (r = 0.99). 3. Coefficients of variation (CV) between individual clearance values for complete vs abbreviated studies averaged 5.5%, 5.8% and 2.9%, and CVs were less than 15% in 95.8%, 93.7% and 98.9% of subjects, respectively, for methods A, B, and C. 4. Overall mean values of elimination half-life (11.9, 12.1, 12.0 and 12.5 h) and volume of distribution (43.7, 45.1, 45.2, and 44.71) were likewise very similar for complete A, B and C analyses respectively. 5. The best correlation with the complete study was observed for the 8 and 24 h sampling scheme, for which clearance values were within 5% of the reference method in 84% of subjects, and within 10% in 97% of subjects. 6. Antipyrine pharmacokinetic parameters can be estimated with reasonable precision using a simplified two-point blood sampling procedure following a single intravenous dose. Estimates of elimination half-life, volume of distribution and clearance based on 8 h and 24 h data points correlated best with complete pharmacokinetic studies.
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Selected References
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