Pharmacokinetics of Lornoxicam in rabbits after single intravenous bolus and intramuscular administrations
-
2016-04-26 https://doi.org/10.14419/ijpt.v4i1.5998 -
Lornoxicam, Pharmacokinetics, Intravenous, Intramuscular, Rabbits. -
Abstract
The pharmacokinetics of lornoxicam (a non-steroidal anti-inflammatory drug) at a dose of 0.4 mg/Kg body weight was evaluated after single intravenous (i.v.) and intramuscular (i.m.) bolus administrations in rabbits. An HPLC assay using pure lornoxicam base as a standard was used to measure its concentrations in plasma at prefixed time points up to 12 hours post administration. Following an i.v. bolus injection, the plasma concentration-time curves of lornoxicam were best represented by two-compartment open model. The drug was rapidly distributed and moderately eliminated with half-lives of distribution (t1/2α) and elimination (t1/2β) of 0.238 and 2.611 h, respectively. The volume of distribution was large with (Vdss) value of 1.499 L. The total body clearance (ClB) was 0.413 L/h. After i.m. bolus administration of the same dose, lornoxicam was moderately and completely absorbed in rabbits with an absorption half-life (t½ab) of 1.228 h with peak plasma concentration (Cmax) of 0.463 μg/mL attained at 1.512 h (Tmax) and systemic bioavailability of 99.79%. The elimination half-life following i.m. administration was 2.283 h. The extent of plasma protein binding percent was 98.9%. The study recommends the use of lornoxicam in rabbits because of its good pharmacokinetic profile indicated by good absorption, bioavailability and plasma concentrations.
-
References
[1] Baggot J 1995, Pharmacokinetics: disposition and fate of drugs in the body. Veterinary pharmacology and therapeutics 18-52.
[2] Baggot JD 1977, Principles of drug disposition in domestic animals: the basis of veterinary clinical pharmacology: WB Saunders.
[3] Baggot JD 1978a, Some aspects of clinical pharmacokinetics in veterinary medicine II. Journal of Veterinary Pharmacology and Therapeutics 1, 111-118. http://dx.doi.org/10.1111/j.1365-2885.1978.tb00314.x.
[4] Baggot JD 1978b, Some aspects of clinical pharmacokinetics in veterinary medicine. I. Journal of Veterinary Pharmacology and Therapeutics 1, 5-18. http://dx.doi.org/10.1111/j.1365-2885.1978.tb00300.x.
[5] Balfour JA, Fitton A & Barradell LB 1996, Lornoxicam. A review of its pharmacology and therapeutic potential in the management of painful and inflammatory conditions. Drugs 51, 639-657. http://dx.doi.org/10.2165/00003495-199651040-00008.
[6] Bhandari S & Khisti N 2012, Extraction-less high-performance liquid chromatographic method for determination of lornoxicam in human plasma. Asian Journal of Pharmaceutical and Clinical Research 5, 122-124.
[7] Botting JH 1999, Nonsteroidal antiinflammatory agents. Drugs Today 35, 225. http://dx.doi.org/10.1358/dot.1999.35.4-5.552199.
[8] Copeland RA, Williams JM, Giannaras J, Nurnberg S, Covington M, Pinto D, Pick S & Trzaskos JM 1994, Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase. Proceedings of the National Academy of Sciences 91, 11202-11206. http://dx.doi.org/10.1073/pnas.91.23.11202.
[9] Craig W & Suh B 1991, Protein binding and the antimicrobial effects: methods for the determination of protein binding. Antibiotics in laboratory medicine Williams & Wilkins, Baltimore, Md 367-402.
[10] Dorrestein GM 1991, The pharmacokinetics of avian therapeutics. Veterinary Clinics of North America: Small Animal Practice 21, 1241-1264. http://dx.doi.org/10.1016/S0195-5616(91)50135-2.
[11] El Dareer SM, Noker PE & and Galbraith WM 1990, Disposition of [14C] lornoxicam in male and female cynomolgus monkeys dosed orally or intravenously. The FASEB Journal 4, A461 (Abstr. 1132).
[12] Grizzle JE 1965, The two-period change-over design and its use in clinical trials. Biometrics 467-480. http://dx.doi.org/10.2307/2528104.
[13] Heeb H, Chun R, Koch D, Goatley M & Hunter R 2003, Single dose pharmacokinetics of piroxicam in cats. Journal of Veterinary Pharmacology and Therapeutics 26, 259-263. http://dx.doi.org/10.1046/j.1365-2885.2003.00479.x.
[14] Heintz R, Guentert T, Enrico J, Dubach U, Brandt R & Jeunet F 1983, Pharmacokinetics of tenoxicam in healthy human volunteers. European Journal of Rheumatology and Inflammation 7, 33-44.
[15] Hitzenberger G, Radhofer-Welte S, Takacs F & Rosenow D 1989, Pharmacokinetics of lornoxicam in man. Postgraduate Medical Journal 66, S22-27.
[16] Kölle E & Vollmer K-O 1986, Pharmacokinetics of isoxicam following intravenous, intramuscular, oral and rectal administration in healthy volunteers. British Journal of Clinical Pharmacology 22, 135S. http://dx.doi.org/10.1111/j.1365-2125.1986.tb02995.x.
[17] Liang Y, Shi Q & Zhou Y-w 2006, Pharmacokinetics and bioequivalence of lornoxicam tablet in healthy volunteers. Chinese Journal of Clinical Pharmacology 22, 336.
[18] Lirk P, Seymour R-A, Ong C-K-S & Tan C-H 2007, An evidence-based update on nonsteroidal anti-Inflammatory Drugs. Clin Med Res 5, 19-34. http://dx.doi.org/10.3121/cmr.2007.698.
[19] Merck-Veterinary-Manual 2016, Nonsteroidal antiinflammatory drugs. Available at http://www.merckvetmanual.com/mvm/pharmacology/anti-inflammatory_agents/nonsteroidal_anti-inflammatory_drugs.html.
[20] Pabst G & Jaeger H 1990, Review of methods and criteria for the evaluation of bioequivalence studies. European Journal of Clinical Pharmacology 38, 5-10. http://dx.doi.org/10.1007/BF00314794.
[21] Paget G & Barnes J 1964, Toxicity tests. Evaluation of drug activities: Pharmacometrics 1, 135.
[22] Prasad Byrav D, Medhi B, Prakash A, Patyar S & Wadhwa S 2009, Lornoxicam: a newer NSAID. IJPMR 20, 27-31.
[23] Radhofer-Welte S & Rabasseda X 2000, Lornoxicam, a new potent NSAID with an improved tolerability profile. Drugs Today 36, 55-76. http://dx.doi.org/10.1358/dot.2000.36.1.566627.
[24] Riegelman S, Loo J & Rowland M 1968, Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit properties of a single compartment. Journal of Pharmaceutical Sciences 57, 117-123. http://dx.doi.org/10.1002/jps.2600570123.
[25] Riggs DS 1964, The Mathematical Approach to Physiological Problems. Academic Medicine 39, 235.
[26] Rosenbaum SE 2012, Basic pharmacokinetics and pharmacodynamics: An integrated textbook and computer simulations: John Wiley & Sons.
[27] SPSS IBM 2011, Version 20. New York, NY, USA: IBM Incorporation.
[28] Watkins J & Klaassen CD 1986, Xenobiotic biotransformation in livestock: comparison to other species commonly used in toxicity testing. Journal of Animal Science 63, 933-942.
[29] Zhang Y, Zhong D, Si D, Guo Y, Chen X & Zhou H 2005, Lornoxicam pharmacokinetics in relation to cytochrome P450 2C9 genotype. British Journal of Clinical Pharmacology 59, 14-17. http://dx.doi.org/10.1111/j.1365-2125.2005.02223.x.
-
Downloads
-
How to Cite
El-Mahmoudy, A. (2016). Pharmacokinetics of Lornoxicam in rabbits after single intravenous bolus and intramuscular administrations. International Journal of Pharmacology and Toxicology, 4(1), 66-73. https://doi.org/10.14419/ijpt.v4i1.5998Received date: 2016-03-12
Accepted date: 2016-04-11
Published date: 2016-04-26