Further observations on relationships between antipyrine half-life, clearance and volume of distribution: an appraisal of alternative kinetic parameters used to assess the elimination of antipyrine.

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The pharmacokinetics of antipyrine have been reassessed to establish more firmly the relative utility of antipyrine half-life and disposition rate constant as indices of antipyrine metabolic clearance rate. Pharmacokinetic analyses were performed from previously published studies on healthy volunteers. In addition healthy, non-smoking, non-obese male volunteers (109 from Hershey, PA and 31 from Bristol, UK) and groups of patients with various forms of liver disease were investigated. For any given apparent volume of distribution, the relationship of clearance and disposition rate constant is linear, whereas the relationship between clearance and half-life is hyperbolic. However, over the range of values commonly observed in healthy volunteers for antipyrine clearance, the relationship between antipyrine clearance and half-life approximates linearity. Over the entire range of values for antipyrine clearance, linearity emerges when either I/t1/2 or the disposition rate constant is plotted against clearance.