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Simplified approaches to the determination of antipyrine pharmacokinetic parameters.
Author(s) -
Scavone JM,
Greenblatt DJ,
Blyden GT,
Harmatz JS,
Graziano PJ
Publication year - 1988
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1988.tb05255.x
Subject(s) - pharmacokinetics , volume of distribution , chemistry , half life , distribution (mathematics) , chromatography , mathematics , medicine , pharmacology , mathematical analysis
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.