Abstract
Influence of two newly synthesized bile acids derivates, namely sodium salt of monoketocholic acid MKH-Na and methyl ester of monoketocholic acid MKH-Me on tramadol (12.5 mg/kg oral and intramuscular) analgesic effect was examined in this research. Analgesic effect was measured by antinociceptive hot plate method. Interaction was estimated by detection of changes in analgesic effect of tramadol combined with bile acids (subcutaneous administration of 4 mg/kg 20 min before tramadol) compared to analgesic effect of the same dose of tramadol given alone. Hydrosoluble sodium salt of monoketocholic acid did not show interaction with tramadol, regardless of the route of administration of tramadol. However, methyl ester of monoketocholic acid increased the analgesic effect of tramadol when it was given intramuscularly. After oral administration of tramadol, methyl ester of monoketocholic acid decreased the analgesic effect of tramadol. According to the time point when interaction reached statistically significant difference, it can be presumed that after intramuscular administration of tramadol, methyl ester of monoketocholic acid increases tramadol absorption and transport to brain and in that way increases its analgesic effect. The analgesic effect of tramadol after oral administration was decreased, which could be explained by the induction of tramadol metabolism in the liver, but should be examined in more details.
Similar content being viewed by others
References
Al-Salami H, Butt G, Tucker I, Mikov M (2008) Influence of semisynthetic bile acid (MKC) on the ileal permeation of gliclazide in healthy and diabetic rats. Pharmacol Rep 60:532–541
Binder HJ, Rawlins CL (1973) Effect of conjugated dihydroxy bile salts on electrolyte transport in rat colon. J Clin Invest 52(6):1460–1466
Dayer P, Desmeules J, Collart L (1997) Pharmacologie du tramadol. Drugs 53(Suppl. 2):18–24
Dobbins JW, Binder HJ (1976) Effect of bile salts and fatty acids on the colonic absorption of oxalate. Gastroenterology 70(6):1096–1100
Freye E, Latasch L, Bredow G, Neruda B (1998) Das Opioid Tramadol hat zentral-exzitatorische Effekte von nicht-opioidartigem Charakter. Der Schmerz 12(1):19–24
Grond S, Sablotzki A (2004) Clinical pharmacology of tramadol. Clin Pharmacokinet 43(13):879–923
Helenius A, Simons K (1975) Solubilization of membranes by detergents. Biochim Biopshys Acta 415:29–79
Hills BA (1979) Possible role of adsorbed surfactant in controlling membrane permeability and function. Med Hypotheses 28:85–92
Hsiesh DS (1994) In: Hsiesh DS (ed) Drug permeation enhancement: theory and applications. Marcel Dekker, New York
Kramer W, Wess G, Neckermann G, Schubert G, Fink J, Girbig F, Gutjahr U, Kowalewski S, Baringhaus KH, Boger G, Enhsen A, Falk E, Friedrich M, Glombik H, Hoffmann A, Pittius C, Urmannc M (1994) Intestinal absorption of peptides by coupling to bile acids. J Biol Chem 269(14):10621–10627
Mikov M, Fawcett JP (2008) In: Mikov M, Fawcett JP (eds) Bile acids–chemistry, biosynthesis, analysis, chemical and metabolic transformation and pharmacology. Mediset-Publishers, Geneva (Switzerland)
Mikov M, Vasovic V, Jakovljevic V, Kveresan S, Kuhajda S (2004) 3α, 7α-Dihydroxy-12-Oxo-5β-cholanate as blood–brain barrier permeator. Pol J Pharmacol 56(3):367–371
Paar WD, Frankus P, Dengler HJ (1992) The metabolism of tramadol by human liver microsomes. Clin Invest 70:708–710
Paar WD, Poche S, Gerloff J, Dengler HJ (1993) In vivo investigation of the metabolism of tramadol: further evidence for O-demethylation polymorphism. Naunyn Schmiedebergs Arch Pharmacol 347:154
Petzinger E, Wickboldt A, Pagels P, Starke D, Kramer W (1999) Hepatobiliary transport of bile acid amino acid, bile acid peptide, and bile acid oligonucleotide conjugates in rats. Hepatology 30:1257–1268
Posa M, Kevresan S, Mikov M, Cirin-Novta V, Kuhajda K (2007) Effect of cholic acid and its keto derivates on the analgesic action of lidocaine and associated biochemical parameters in rats. Eur J Drug Metab Pharmacokinet 32(2):109–117
Posa M, Guzsvany V, Csanadi J, Kevresan S, Kuhjada K (2008) Formation of hydrogen-bonded complexes between bile acids and lidocaine in the lidocaine transfer from an aqueous phase to chloroform. Eur J Pharm Sci 34:281–292
Raskovic A, Mikov M, Skrbic R, Jakovljevic V, Vasovic V, Posa M, Kuhajda K, Kevresan S, Tomic Z, Siladji D (2008) Effect of stevioside and sodium salt of monoketocholic acid on glycemia in normoglycemic and diabetic rats. Eur J Drug Metab Pharmacokinet 33(1):17–22
Sayani AP, Chien YW (1996) Systemic delivery of peptides and proteins across absorptive mucosae. Crit Rev Ther Drug Carrier Syst 13(1–2):85–184
Subrahmanyam V, Renwick AB, Walters DG, Young PJ, Price RJ, Tonelli AP, Lake BG (2001) Identification of cytochrome p-450 isoforms responsible for Cis-tramadol metabolism in human liver microsomes. Drug Metab Dispos 29(8):1146–1155
Tominaga S, Watanabe A, Tsuji T (1991) Synergistic effect of bile acid, endotoxin, and ammonia on brain edema. Metab Brain Dis 6:93–105
Vasovic V, Mikov M, Kuhajda K, Kevresan S, Jakovljevic V (2001) The influence of sodium salt of monoketocholic acid on quinine transport into the central nervous system in rats. Iugosl Physiol Pharmacol Acta 37(3):89–98
Vogel G, Vogel WH (1997) Drug discovery and evaluation: pharmacological assays, 1st edn. Springer, Berlin
Wahler JB, Swain MG, Carson R, Bergasa NV, Jones E (1993) Blood–brain barrier permeability is markedly decreased in cholestasis in the rat. Hepatology 17:1103–1108
Acknowledgments
This research was performed with the financial support from the National Ministry of Science, Republic of Serbia within project No. 145060.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Vasovic, V., Vukmirovic, S., Pjevic, M. et al. Influence of bile acid derivates on tramadol analgesic effect in mice. Eur J Drug Metab Pharmacokinet 35, 75–78 (2010). https://doi.org/10.1007/s13318-010-0011-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13318-010-0011-z