and without renal failure. British Journal of Anaesthesia 53: 1049-1053,1981 Fuseau E, Sheiner LB. Simultaneous modeling of pharmacokinetics and pharmacodynamics with a nonparametric pharmacodynamic model. Clinical Pharmacology and Therapeutics 35: 733-741, 1984 Gibaldi M, Perrier D. Pharmacokinetics. In Drugs and the pharmaceutical sciences, 2nd ed., Vol. 15, pp. 409-417, 445-449, Marcel Dekker Inc, New York, 1982 Hennis PJ, Stanski DR. Pharmacokinetic and pharmacodynamic factors that govern the clinical use of muscle relaxants. Seminars in Anesthesia 4: 21-30, 1985 Holford NHG, Sheiner LB. Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clinical Pharmacokinetics 6: 429-453, 1981 Lebrault C, Berger JL, D'Hollander AA, Gomeni R, Henzel D, et aL Pharmacokinetics and pharmacodynamics of vecuronium (ORG NC 45) in patients with cirrhosis. Anesthesiology 62: 601-605, 1985 Lebrault C, Duvaldestin P, Henzel D, Chauvin M, Guesnon P. Pharmacokinetics and pharmacodynamics of vecuronium in patients with cholestasis. British Journal of Anaesthesia 58: 983-987, 1986 Lien CA, Matteo RS, Ornstein E, Schwartz RS, Diaz J. Distribution, elimination, and action of vecuronium in the elderly. Anesthesia and Analgesia 72: 811-816, 1991 Lynam DP, Cronnely R, Castagnoli KP, Canfell PC, Caldwell J, et aL The pharmacodynamics and pharmacokinetics of vecuronium in patients anesthetized with isoflurane with normal renal function or with renal failure. Anesthesiology 69: 227231, 1988 Meistelman C, Lienhart A, Leveque C, Bitker MO, Pigot B, et al. Pharmacology ofvecuronium in patients with end-stage renal failure. European Journal of Anaesthesiology 3: 153-158, 1986 Minsaas B, Stovner J. Artery-to-muscle onset time for neuromuscular blocking drugs. British Journal of Anaesthesia 52: 403-407, 1980 Rupp SM, Castagnoli KP, Fisher OM, Miller RO. Pancuronium and vecuronium pharmacokinetics and pharmacodynamics in younger and elderly adults. Anesthesiology 67: 45-49, 1987 Savage OS, Sleigh T, Carlyle I. The emergence ofOrg NC 45 from the pancuronium series. British Journal of Anaesthesia 52 (Suppl. I): 3S-IOS, 1980
Clin. Pharmacokinet. 24 (6) 1993
Schwarz G. Estimating the dimension of a model. Annals of Statistics 6: 461-464, 1978 Segredo V, Shin YS, Sharma ML, Gruenke LO, Caldwell JE, et al. Pharmacokinetics, neuromuscular effects, and biodisposition of 3-desacetylvecuronium (Org 7268) in cats. Anesthesiology 74: 1052-1059, 1991 Shafer SL, Varvel JR, Gronert GA. A comparison of parametric with semi parametric analysis of the concentration versus effect relationship of metocurine in dogs and pigs. Journal of Pharmacokinetics and Biopharmaceutics 17: 291-304,1989 Shanks CA, Avram MJ, Fragen RJ, O'Hara OA. Pharmacokinetics and pharmacodynamics of vecuronium administered by bolus and infusion during halothane or balanced anaesthesia. Clinical Pharmacology and Therapeutics 42: 459-464, 1987 Sheiner LB, Stanski DR, Vozeh S, Miller RO, Ham J. Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clinical Pharmacology and Therapeutics 25: 358-371, 1979 Sohn YJ, Bencini A, Scaf AHJ, Kersten U, Agoston S. Comparative pharmacokinetics and dynamics of vecuronium and pancuronium in anesthetized patients. Anesthesia and Analgesia 65: 233-239, 1986 Unadkat JO, Bartha F, Sheiner LB. Simultaneous modeling of pharmacokinetics and pharmacodynamics with non parametric kinetic and dynamic models. Clinical Pharmacology and Therapeutics 40: 86-93, 1986 Van der Veen F, Bencini A. Pharmacokinetics and pharmacodynamics ofOrg NC 45 in man. British Journal of Anaesthesia 52 (Suppl. I): 37S-4IS, 1980 Van Rossum JM, De Bie JEGM, Van Lingen G, Teeuwen HWA. Pharmacokinetics from a dynamical systems point of view. Journal of Phal1"acokinetics and Biopharmaceutics 17: 365392, 1989 Yamaoka K, Nakagawa T, Uno T. Application of Akaike's Information Criterion (AIC) in the evaluation of linear pharmacokinetic equations. Journal of Pharmacokinetics and Biopharmaceutics 6: 165-175, 1978
Correspondence and reprints: Or France Varin. Associate Professor, Faculte de Pharmacie, Universite de Montreal, Succ. A, c.P. 6128, Montreal, Quebec, H3C 3J7, Canada.
Erratum Vol. 24, No.3, page 195: The first 2 paragraphs of the Summary should be replaced with the following text: 'Simvastatin is a methyl analogue of lovastatin and acts as an HMG-CoA reductase inhibitor effective in the treatment of hypercholesterolaemia. Like lovastatin, it is an inactive hydrophobic lactone prodrug which is metabolised in vivo to several more polar, pharmacologically active compounds, most notably the corresponding hydroxy acid form, simvastatin acid. 'HPLC techniques have been developed to assay simvastatin and its metabolites. In addition, a pharmacodynamic assay has been developed that measures HMG-CoA reductase inhibitory activity. This latter assay may be more applicable to clinical situations since simvastatin is not active, while its metabolites are.'