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Clinical Pharmacokinetics Pethidine

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Abstract

Pethidine is commonly used in single doses as a preoperative medication or in multiple doses as an analgesic. The clinical consequences of altered disposition are more likely to result from its analgesic use. Correlations between plasma pethidine concentration, analgesia and side effects such as respiratory depression, have been established, but considerable overlap exists between concentrations producing therapeutic and non-therapeutic effects. The current practice of intermittent pethidine administration (intravenous, intramuscular and oral) for analgesia results in fluctuations in pethidine plasma concentrations which are associated with incomplete pain relief and side effects. Continuous intravenous infusion of pethidine may avoid these difficulties.

Changes in pethidine disposition have been observed in patients with liver disease and in the elderly. Measurement of plasma pethidine concentrations may be helpful as an aid to the management of such patients. In renal disease, metabolites may accumulate and cause side effects.

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References

  • A.Ph.A. Steering Committee for the Evaluation of Drug Interactions: Evaluation of Drug Interactions, 2nd Ed, p. 142–144 (American Pharmaceutical Association, Washington DC 1976).

    Google Scholar 

  • Asatoor, A.M.; London, D.R.; Milne, M.D. and Simenhoff, M.L.: The excretion of pethidine and its derivatives. British Journal of Pharmacology 20: 285–298 (1963).

    CAS  Google Scholar 

  • Beaver, W.T. and Feise, G.: Comparison of the analgesic effects of morphine, hydroxyzine, and their combination in patients with postoperative pain; in Bonica and Albe-Fessard (Eds) Advances in Pain Research and Therapy, vol. I, p.553–557 (Raven Press, New York 1976).

    Google Scholar 

  • Beckett, A.H. and Taylor, J.F.: Blood concentrations of pethidine and pentazocine in mother and infant at time of birth. Journal of Pharmacy and Pharmacology 19 (Suppl): 50S–52S (1967).

    PubMed  Google Scholar 

  • Bellville, J.W.; Forrest, W.H.; Miller, E. and Brown, B.W.: Influence of age on pain relief from analgesics. Journal of the American Medical Association 217: 1835–1841 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Blaschke, T.F.: Protein binding and kinetics of drugs in liver disease. Clinical Pharmacokinetics 2: 32–44 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Blaschke, T.F.; Neal, E.A. and Meffin, P.J.: Increased bioavailability and decreased clearance of analgesics in patients with cirrhosis. Abstract, 7th International Congress of Pharmacology, Paris, July 16-21 (1978).

    Google Scholar 

  • Brackbill, Y.; Kane, J.; Maniello, R.L. and Abramson, D.: Obstetric meperidine usage and assessment of neonatal status. Anesthesiology 40: 116–120 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Burns, J.J.; Berger, B.L.; Lief, P.A.; Wollack, A.; Papper, E.M. and Brodie, B.D.: The physiological disposition and fate of meperidine (Demerol) in man and a method for its estimation in plasma. Journal of Pharmacology and Experimental Therapeutics 114: 289–298 (1955).

    PubMed  CAS  Google Scholar 

  • Caldwell, J.; Wakile, L.A.; Notarianni, L.J.; Smith, R.L.; Correy, G.J.; Lieberman, B.A.; Beard, R.W.; Finnie, M.D.A. and Snedden, W.: Maternal and neonatal disposition of pethidine in childbirth — a study using quantitative gas chromatography — mass spectrometry. Life Sciences 22: 589–596 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Chan, K.; Kendall, M.J. and Mitchard, M.: A quantitative gas-liquid Chromatographic method for the determination of pethidine and its metabolites, norpethidine and pethidine N-oxide in human biological fluids. Journal of Chromatography 89: 169–176 (1974).

    Article  CAS  Google Scholar 

  • Chan, K.; Kendall, M.J.; Wells, W.D.E. and Mitchard, M.: Factors influencing the excretion and relative physiological availability of pethidine in man. Journal of Pharmacy and Pharmacology 27: 235–241 (1975a).

    Article  PubMed  CAS  Google Scholar 

  • Chan, K.; Kendall, M.J.; Mitchard, M. and Wells, W.D.E.: The effect of ageing on plasma pethidine concentration. British Journal of Clinical Pharmacology 2: 297–302 (1975b).

    Article  PubMed  CAS  Google Scholar 

  • Cooper, L.V.; Stephen, G.W. and Aggett, P.J.A.: Elimination of pethidine and bupivacaine in the newborn. Archives of Disease in Childhood 52: 638–641 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Crawford, J.S.: Principles and practice of obstetric anaesthesia. 3rd Ed. p.75 (Blackwell, Oxford 1972).

    Google Scholar 

  • Crawford, J.S. and Rudofsky, S.: The placental transmission of pethidine. British Journal of Anaesthesia 37: 929–933 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Crawford, J.S. and Rudofsky, S.: Some alterations in the pattern of drug metabolism associated with pregnancy, oral contraceptives and the newly-born. British Journal of Anaesthesia 38: 446–454 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Downes, J.J.; Kemp, R.A. and Lambertsen, C.J.: The magnitude and duration of respiratory depression due to fentanyl and meperidine in man. Journal of Pharmacology and Experimental Therapeutics 158: 416–420 (1967).

    PubMed  CAS  Google Scholar 

  • Dubowitz, V.: Neurological fragility in the newborn. British Journal of Anaesthesia 47: 1005–1010 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Dundee, J.W.; Clarke, R.S.J. and Loan, W.B.: A comparison of the sedative and toxic effects of morphine and pethidine. Lancet 2: 1262–1263 (1965).

    Article  Google Scholar 

  • Dunkerley, R.; Johnson, R.; Schenker, S. and Wilkinson, G.R.: Gastric and biliary excretion of meperidine in man. Clinical Pharmacology and Therapeutics 20: 546–551 (1976).

    PubMed  CAS  Google Scholar 

  • Eade, N.R. and Renton, K.W.: Effect of monoamine oxidase inhibitors on the N-demethylation and hydrolysis of meperidine. Biochemical Pharmacology 19: 2243–2250 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Economou, G. and Ward-McQuaid, J.N.: A cross-over comparison of the effect of morphine, pethidine, pentazocine and phenazocine on biliary pressure. Gut 12: 218–221 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Eisleb, V.O. and Schaumann, O.; Dolantin, ein neuartiges Spasmolytikum und analgetikum (Chemisches und Pharmakologisches). Deutsche Medizinische Wochenschrift 65: 967–968 (1939).

    Article  CAS  Google Scholar 

  • Evans, M.A. and Harbison, R.D.: Micromethod for determination of meperidine in plasma. Journal of Pharmaceutical Sciences 66: 598–600 (1977).

    Google Scholar 

  • Evans, G.H. and Shand, D.G.; Disposition of Propranolol. VI. Independent variation in steady-state circulating drug concentrations and half-life as a result of plasma drug binding in man. Clinical Pharmacology and Therapeutics 14: 494–500 (1973).

    PubMed  CAS  Google Scholar 

  • Freeman, D.S.; Gjika, H.B. and Van Vunakis, H.: Radioimmunoassay for normeperidine: Studies on the N-dealkylation of meperidine and anileridine. Journal of Pharmacology and Experimental Therapeutics 203: 203–212 (1977).

    PubMed  CAS  Google Scholar 

  • Fung, D.L.; Eisele, J.H.; Asling, J.H. and Martucci, R.W.: The respiratory response to CO, following intravenous meperidine in man. Abstracts of Scientific Papers, American Society of Anesthesiologists. Annual Meeting, p.257–258 (1975).

  • Gessner, P.K.; Clarke, C.C. and Adler, M.: The effect of low environmental temperature on the tranylcypromine-meperidine interaction in mice. Journal of Pharmacology and Experimental Therapeutics 189: 90–96 (1974).

    PubMed  CAS  Google Scholar 

  • Gessner, T.; Trudnoswki, R.; Rico, R. and Rempel, J.: Passage of intravenously administered pethidine into gastric juice in humans. Journal of Pharmacy and Pharmacology 28: 78–81 (1976).

    Article  Google Scholar 

  • Goehl, T.J. and Davison, C.: GLC Determination of meperidine in blood plasma. Journal of Pharmaceutical Sciences 62: 907–909 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Hartvig, P.; Karlsson, K.-E.; Lindberg, C. and Boreus, L.O.: Simultaneous determination of therapeutic plasma concentrations of pethidine and norpethidine in man by electron capture gas chromatography. European Journal of Clinical Pharmacology 11: 65–69 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Hogg, M.I.J.; Wiener, P.C.; Rosen, M. and Mapelson, W.W.: Urinary excretion and metabolism of pethidine and norpethidine in the newborn. British Journal of Anaesthesia 49: 891–898 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Jaffe, J.H. and Martin, W.R.: Narcotic analgesics and antagonists; in Goodman and Gilman (Eds) The Pharmacological Basis of Therapeutics, p.245–283 (MacMillan, New York 1975).

    Google Scholar 

  • Kanton, TG. and Steinberg, F.P.: Studies of tranquilizing agents and meperidine in clinical pain. Hydroxyzine and meprobamate; in Bonica and Albe-Fessard (Eds) Advances in Pain Research and Therapy, vol. 1, p.567–572 (Raven Press, New York 1976).

    Google Scholar 

  • Keats, A.S.; Telford, J. and Kurosu, Y.: ‘Potentiation’ of meperidine by Promethazine. Anesthesiology 22: 34–41 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Keats, A.S. and Girgis, K.Z.: Respiratory depression associated with relief of pain by narcotics. Anesthesiology 29: 1006–1013 (1968).

    PubMed  CAS  Google Scholar 

  • Keeri-Szanto, M. and Heaman, S.: Postoperative demand analgesia. Surgery, Gynecology and Obstetrics 134: 647–651 (1972).

    PubMed  CAS  Google Scholar 

  • Klotz, U.; McHorse, T.S.; Wilkinson, G.R. and Schenker, S.: The effect of cirrhosis on the disposition and elimination of meperidine in man. Clinical Pharmacology and Therapeutics 16: 667–675 (1974).

    PubMed  CAS  Google Scholar 

  • Korttila, K. and Linnoila, M.: Psychomotor skills related to driving after intramuscular administration of diazepam and meperidine. Anesthesiology 42: 685–691 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Koska, A.J.; Kramer, W.G.; Romagnoli, A. and Keats, A.S.: High-dose pharmacokinetics of meperidine in surgical patients. Clinical Pharmacology and Therapeutics 23: 116–117 (1978).

    Google Scholar 

  • Lindberg, C.; Bogentoft, C. and Danielsson, B.: Mass spectrometry of pethidine and pethidine metabolites. Acta Pharmaceutica Suecica 11: 201–210 (1974).

    PubMed  CAS  Google Scholar 

  • Loeschke, H.H.; Sweel, A.; Kough, R.H. and Lambertsen, C.J.: The effect of morphine and of meperidine (Dolantin, Demerol) upon the respiratory response of normal men to low concentrations of inspired carbon dioxide. Journal of Pharmacology and Experimental Therapeutics 108: 376–383 (1953).

    Google Scholar 

  • Lundbergh, P. and Strandell, T.: Changes in hepatic circulation at rest, driving and after exercises in young males with infectious hepatitis compared to controls. Acta Medica Scandinavica 196: 315–325 (1974).

    Article  PubMed  CAS  Google Scholar 

  • MacDonald, A.D.; Woolfe, G.; Bergel, F.; Orrison, A.L. and Rinderknecht, H.; Analgesic action of pethidine derivatives and related compounds. Brit. J. Pharmacol. 1: 4–14 (1946).

    CAS  Google Scholar 

  • McHorse, T.S.; Wilkinson, G.R.; Johnson, R.F. and Schenker, S.: Effect of acute viral hepatitis in man on the disposition and elimination of meperidine. Gastroenterology 68: 775–780 (1975).

    PubMed  CAS  Google Scholar 

  • Mather, L.E.: Pharmacokinetics of meperidine in man. Clinical Pharmacology and Therapeutics 19: 246–247 (1976).

    Google Scholar 

  • Mather, L.E.; Tucker, G.T.; Pflug, A.E.; Lindop, M.J. and Wilkerson, C.: Meperidine kinetics in man. Clinical Pharmacology and Therapeutics 17: 21–30 (1975a).

    PubMed  CAS  Google Scholar 

  • Mather, L.E.; Lindop, M.J.; Tucker, G.T. and Pflug, A.E.: Pethidine revisited: Plasma concentrations and effects after intramuscular injection. British Journal of Anaesthesia 47: 1269–1275 (1975b).

    Article  PubMed  CAS  Google Scholar 

  • Mather, L.E.; Stapleton, J.V. and Austin, K.L.: A rational approach to post-operative pain control — at last? Clinical Pharmacology and Therapeutics 23: 121 (1978).

    Google Scholar 

  • Mather, L.E. and Tucker, G.T.: Meperidine and other basic drugs: General method for their determination in plasma. Journal of Pharmaceutical Sciences 63: 306–307 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Mather, L.E. and Tucker, G.T.: Systemic availability of orally administrated meperidine. Clinical Pharmacology and Therapeutics 20: 535–540 (1976).

    PubMed  CAS  Google Scholar 

  • Miller, J.W. and Anderson, H.H.: The effect of N-demethylation on certain pharmacologic actions of morphine, codeine and meperidine in the mouse. Journal of Pharmacology and Experimental Therapeutics 112: 191–196 (1954).

    PubMed  CAS  Google Scholar 

  • Moore, J.; McNabb, T.G. and Glynn, J.P.: The placental transfer of pentazocine and pethidine. British Journal of Anaesthesia 45 (Suppl.): 798–801 (1973).

    PubMed  Google Scholar 

  • Moore, G. and Nation, R.: Pharmacokinetics of meperidine in man. Clinical Pharmacology and Therapeutics 19: 246 (1976).

    PubMed  CAS  Google Scholar 

  • Morgan, D.; Moore, G.; Thomas, J. and Triggs, E.: The disposition of meperidine in pregnancy. Clinical Pharmacology and Therapeutics 23: 288–295 (1978).

    PubMed  CAS  Google Scholar 

  • Morrison, J.C.; Wiser, W.L.; Rosser, S.I.; Gayden, J.O.; Bucovaz, E.T.; Whybrew, W.D. and Fish, S.A.: Metabolites of meperidine related to fetal depression. American Journal of Obstetrics and Gynecology 115: 1132–1137 (1973).

    PubMed  CAS  Google Scholar 

  • Morrison, J.C.; Whybrew, W.D.; Rosser, S.I.; Bucovaz, E.T.; Wiser, W.L. and Fish, S.A.: Metabolites of meperidine in the fetal and maternal serum. American Journal of Obstetrics and Gynecology 126: 997–1002 (1976).

    PubMed  CAS  Google Scholar 

  • Muneyuki, M.; Ueda, Y.; Urabe, N.; Takeshita, H. and Inamoto, A.: Post-operative pain relief and respiratory function in man. Anesthesiology 29: 304–313 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Nadasdi, M. and Zsotér, T.T.: The effect of meperidine on the peripheral circulation. Clinical Pharmacology and Therapeutics 10: 239–243 (1969).

    PubMed  CAS  Google Scholar 

  • Nies, A.S.; Shand, D.G. and Wilkinson, G.R.: Altered hepatic blood flow and drug disposition. Clinical Pharmacokinetics 1: 135–155 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Nimmo, W.S.: Drugs, diseases and altered gastric emptying. Clinical Pharmacokinetics 1: 189–203 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Nimmo, W.S.. Wilson, J. and Prescott, L.F.: Narcotic analgesics and delayed gastric emptying during labour. Lancet I: 890–892 (1975).

    Article  Google Scholar 

  • Rogers, K.J. and Thornton, J.A.: The interaction between monoamine oxidase inhibitors and narcotic analgesics in mice. British Journal of Pharmacology 36: 470–480 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Rowland, M.; Blaschke, T.F.; Meffin, P.J. and Williams, R.L.: Pharmacokinetics in disease states modifying hepatic and metabolic function in Benet (Ed) The Effect of Disease States on Drug Pharmacokinetics. p.53–75 (American Pharmaceutical Association Academy of Pharmaceutical Sciences, Washington DC 1976).

    Google Scholar 

  • Rowland, M.: Influence of route of administration of drug availability. Journal of Pharmaceutical Sciences 70: 74 (1972).

    Google Scholar 

  • Shih, A.P.L.; Robinson, K. and Au, W.Y.W.: Determination of therapeutic serum concentrations of oral and parenteral meperidine by gas liquid chromatography. European Journal of Clinical Pharmacology 9: 451–456 (1976).

    Article  CAS  Google Scholar 

  • Stambaugh, J.E. and Wainer, I.W.: The bioavailability of meperidine. Journal of Clinical Pharmacology 14: 552–559 (1974).

    PubMed  CAS  Google Scholar 

  • Stambaugh, J.E. and Wainer, I.W.: Drug interactions 1: Meperidine and combination oral contraceptives. Journal of Clinical Pharmacology 15: 46–51 (1975).

    CAS  Google Scholar 

  • Stambaugh, J.E. and Wainer, I.W.: Metabolic studies of hydroxyzine and meperidine in human subjects; in Bonica and Albe-Fessard (Eds) Advances in Pain Research and Therapy, vol. I. p.559–565 (Raven Press. New York 1976).

    Google Scholar 

  • Stambaugh, J.E.; Wainer, I.W.; Sanstead, J.K. and Hemphill, D.M.: The clinical pharmacology of meperidine — comparison of routes of administration. Journal of Clinical Pharmacology 16: 245–256 (1976).

    PubMed  CAS  Google Scholar 

  • Stambaugh, J.E.; Wainer, I.W.; Hemphill, D.M. and Schwartz, I.: A potentially toxic drug interaction between pethidine (meperidine) and phenobarbitone. Lancet 1: 398–399 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Stillwell, W.G. and Myran, C.S.: Meperidine metabolites: Identification of N-hydroxynormeperidine and a hydroxy-methoxy derivative of meperidine in biological fluids. Research Communications in Chemical Pathology and Pharmacology 14: 605–619 (1976).

    PubMed  CAS  Google Scholar 

  • Szeto, H.H.; Inturrisi, C.E.; Houde, R.; Saal, S.; Cheigh, J. and Reidenberg, M.M.; Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure or cancer. Annals of Internal Medicine 86: 738–741 (1977).

    PubMed  CAS  Google Scholar 

  • Van Vunakis, H.: Radioimmunoassay for anileridine, meperidine and other N-substituted phenyl piperidine carboxylic acid esters. Research Communications in Chemical Pathology and Pharmacology 12: 379–387 (1975).

    PubMed  Google Scholar 

  • Wainer, B.H.; Wung, W.E.; Hill, J.H.; Fitch, F.W.; Fried, J. and Rothberg, R.M.: The production and characterisation of antibodies reactive with meperidine. Journal of Pharmacology and Experimental Therapeutics 197: 734–743 (1976).

    PubMed  CAS  Google Scholar 

  • Wainer, I.W. and Stambaugh, J.E.: GLC determination of meperidinic and nor-meperidinic acids in urine. Journal of Pharmaceutical Sciences 67: 116–117 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Way, W.L.; Costley, E.C. and Way, E.L.: Respiratory sensitivity of the newborn infant to meperidine and morphine. Clinical Pharmacology and Therapeutics 6: 454–461 (1965).

    PubMed  CAS  Google Scholar 

  • Wilkinson, G. and Schenker, S.: Pharmacokinetics of meperidine in man. Clinical Pharmacology and Therapeutics 19: 486–488 (1976).

    CAS  Google Scholar 

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  1. Department of Anaesthesia and Intensive Care. Flinders Medical Centre, Flinders University of South Australia, Bedford Park, South Australia, 5042, Australia

    Laurence E. Mather

  2. Department of Clinical Pharmacology. Flinders Medical Centre, Flinders University of South Australia, Bedford Park, South Australia, 5042, Australia

    Peter J. Meffin

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Mather, L.E., Meffin, P.J. Clinical Pharmacokinetics Pethidine. Clin Pharmacokinet 3, 352–368 (1978). https://doi.org/10.2165/00003088-197803050-00002

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