Summary
The pharmacokinetics and metabolism of mepivacaine has been studied in premature neonates dosed subcutaneously and in healthy adults dosed intravenously. The pharmacokinetics of mepivacaine in four neonates (N) was compared with that in six adults (A). Newborns had a significantly longer terminal phase half-life than adults (N mean 8.69 h; A mean 3.17 h). Total plasma clearance normalized on body weight was significantly smaller in neonates (mean 2.34 ml/min/kg) than in adults (mean 5.47 ml/min/kg), as was the hepatic blood clearance (N mean 1.37 ml/min/kg; A mean 5.10 ml/min/kg). The renal plasma clearance, however, was significantly greater in neonates (mean 0.76 ml/min/kg) than adults (mean 0.20 ml/min/kg). There was an average six-fold increase in the fraction of the dose excreted unchanged in newborns (mean 43.3%) compared to adults (mean 7.1%) with acidified urine (pH 5.5–6.0). There was significantly more of the mono-N-demethylated metabolite of mepivacaine excreted by newborns (mean 11.4%) than by adults (mean 2.2%), but their capacity to carry out aromatic hydroxylation of mepivacaine was negligible. These results for mepivacaine were compared with those previously reported for lignocaine in premature infants. The immaturity of hepatic function appears to have diminished more profoundly the ability of premature infants to metabolize mepivacaine than lignocaine. These findings are discussed in terms of perfusion theory of hepatic drug elimination.
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References
Boréus, L. O., Jalling, B., Kållberg, N.: Phenobarbital metabolism in adults and newborn infants. To be published.
Boxenbaum, H. G., Riegelman, S., Elashoff, R. M.: Statistical estimations in pharmacokinetics. J. Pharmacokin. Biopharm.2, 123–148 (1974)
Boyes, R. N.: A review of the metabolism of amide local anaesthetic agents. Brit. J. Anaesth.47, 225–230 (1975)
Brown, W. U., Bell, G. C., Lurie, A. O., Weiss, J. B., Scanlon, J. W., Alper, M. H.: Newborn blood levels of lidocaine and mepivacaine in the first postnatal day following maternal epidural anesthesia. Anesthesiology42, 698–707 (1975)
Goldstein, A.: Biostatistics: An introductory text, pp. 55–58. New York: Macmillan Co. 1964
Loggie, J. M. H., Kleinman, L. I., Van Maanen, E. F.: Renal function and diuretic therapy in infants and children Part I. J. Pediat.86, 485–496 (1975)
Magno, R., Berlin, A., Karlsson, K., Kjellmer, I.: Anesthesia for caesarian section II: Placental transfer and neonatal elimination of bupivacaine following epidural analgesia for elective caesarean section. Acta anaesth. scand.20, 141–146 (1976)
Mcffin, P., Long, G. J., Thomas, J.: Clearance and metabolism of mepivacaine in the human neonate. Clin. Pharmacol. Ther.14, 218–225 (1973)
Metzler, C.: NONLIN Program, Division of Mathematical Services. Kalamazoo, MI: Upjohn Comp. 1969
Mihaly, G. W., Moore, R. G., Thomas, J., Triggs, E. J., Thomas, D., Shanks, C. A.: The pharmacokinetics of the anilide local anaesthetics in neonates. I. Lignocaine. Europ. J. clin. Pharmacol.13, 143–152 (1978)
Morgan, D., McQuillan, D., Thomas, J.: The pharmacokinetics of the anilide local anaesthetics in neonates. II. Etidocaine. Europ. J. clin. Pharmacol.13, 365–371 (1978)
Morishima, H. O., Daniel, S. S., Finster, M., Poppers, P. J., James, L. S.: Transmission of mepivacaine hydrochloride (Carbocaine) across the human placenta. Anesthesiology27, 147–154 (1966)
Parke, D. V.: The Biochemistry of Foreign Compounds, pp 51–52. Oxford: Pergamon Press 1968
Perrier, D., Gibaldi, M.: Clearance and biological half-life as indices of intrinsic hepatic metabolism. J. Pharmacol. Exp. Ther.191, 17–24 (1974)
Riegelman, S., Loo, J. C. K., Rowland, M.: Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. J. Pharm. Sci.57, 117–123 (1968)
Rowland, M., Benet, L. Z., Graham, G. G.: Clearance concepts in pharmacokinetics. J. Pharmacokin. Biopharm.1, 123–136 (1973)
Rowland, M., Thomson, P. D., Guichard, A., Melmon, K. L.: Disposition kinetics of lidocaine in normal subjects. Ann. N. Y. Acad. Sci.179, 383–398 (1971)
Thomas, J., Meffin, P.: Aromatic hydroxylation of lidocaine and mepivacaine in rats and humans. J. Med. Chem.15, 1046–1049 (1972)
Tucker, G. T., Boyes, R. N., Bridenbaugh, P. O., Moore, D. C.: Binding of anilide type local anesthetics in human plasma; I. Relationship between binding, Physicochemical properties and anesthetic activity. Anesthesiology33, 287–303 (1970a) II. Implications in vivo, with special reference to transplacental distribution. Anesthesiology33, 304–314 (1970b)
Tucker, G. T., Mather, L. E.: Pharmacokinetics of local anaesthetic agents. Br. J. Anaesth.47, 213–224 (1975)
Widdowson, E. M.: Growth and composition of the fetus and newborn. In: Biology of gestation. N. S. Assali (ed.), pp 1–44. New York, London: Academic Press 1968
Wilkinson, G. R., Shand, D. G.: A physiological approach to hepatic drug clearance. Clin. Pharmacol. Ther.18, 377–390 (1975)
Yaffe, S. J., Juchau, M. R.: Perinatal pharmacology, Ann. Rev. Pharmacol.14, 219–238 (1974)
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Moore, R.G., Thomas, J., Triggs, E.J. et al. The pharmacokinetics and metabolism of the anilide local anaesthetics in neonates. Eur J Clin Pharmacol 14, 203–212 (1978). https://doi.org/10.1007/BF02089961
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DOI: https://doi.org/10.1007/BF02089961