Summary
The oral absorption of bezitramide 5 mg was studied in 7 human volunteers, using a specific radioimmuno-assay which measured both bezitramide and its active metabolite R-4618. A lag time of 0.5–1.0 h and a Cmax of 5.4 ng/ml plasma were found, the latter occurring 2.5–3.5 h after administration. The apparent elimination half-life varied from 11 to 24 h. Less than 0.3% of the dose was excreted unchanged in the urine. High concentrations in the faeces of some individuals indicate incomplete absorption and/or biliary secretion. The analgesic effect, using a standardized superficial electrical stimulation method, reached its maximum between 2.5 and 3.5 h after dosing, in accordance with the absorption phase. The duration of the effect was highly variable. Experiments in rats (n=6,3H-bezitramide 2.5 µg), demonstrated extensive biliary excretion (up to 70% of total radioactivity) and less than 3% of the label was removed by urinary excretion.
References
Knape H (1970) Bezitramide an orally active analgesic. Br J Anaesth 42: 325–328
Knape H (1971) Further experience with bezitramide. Br J Anaesth 43: 76–83
Admiraal PV, Knape H, Zegveld C (1972) Experience with bezitramide and droperidol in the treatment of severe chronic pain. Br J Anaesth 44: 1191–1196
Amery WKP, Admiraal PV, Beck PHM et al. (1971) Peroral management of chronic pain by means of bezitramide (R-4825), a long acting analgesic and droperidol (R-4749) a neuroleptic. Arzneimittelforsch 21: 868–871
Kay B (1973) A study of strong oral analgesic: the relief of postoperative pain using dextromoramide pentazocine and bezitramide. Br J Anaesth 45: 623–628
Janssen PAJ (1982) Potent new analgesics, tailor-made for different purposes. Acta Anaesth Scand 26: 262–268
Van Rooy HH, Kok M, Modderman E et al. (1978) Determination of the metabolites of bezitramide in urine I. The acidic metabolite. J Chromatogr 148: 447–452
Van Rooy HH, Soe Agnie C (1978) Determination of the metabolites of bezitramide in urine II. The basic metabolite. J Chromatogr 156: 189–195
Janssen PAJ, Niemegeers CJE, Schellekens KHL et al. (1971) Bezitramide (R-4825) a new potent and orally long-acting analgesic compound. Arzneimittelforsch (Drug Res) 21: 862–867
Notermans SLH (1961) Measurement of pain threshold determined by electrical stimulation and its clinical application. Neurology 16: 1071–1086
Lahoda R, Stacher G, Bauer P (1977) Experimentally induced pain measurement of pain threshold and pain tolerance using a new apparatus for electrical stimulation of the skin. Int J Clin Pharmacol 15: 51–56
Ruifrok PG (1982) Automated pharmacokinetic analysis: experiences of a user. Biopharm Drug Dis 3: 243–253
Mulder GJ, Scholtens E, Meijer DKF (1981) Collection of metabolites in bile and urine from the rat. Methods Enzymol 77: 21–30
Paalzow L, Nilsson L, Stenberg P (1982) Pharmacokinetic basis for optimal methadone treatment of pain in cancer patients. Acta Anaesth Scand 26 [Suppl 74] 66–69
Rollins DE, Klaassen CD (1979) Biliary excretion of drugs in man. Clin Pharmacokinet 4: 368–379
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Meijer, D.K.F., Hovinga, G., Versluis, A. et al. Pharmacokinetics of the oral narcotic analgesic bezitramide and preliminary observations on its effect on experimentally induced pain. Eur J Clin Pharmacol 27, 615–618 (1984). https://doi.org/10.1007/BF00556902
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DOI: https://doi.org/10.1007/BF00556902