HPLC Analysis and Bio-kinetics Study of Pyrazinamide in Healthy Volunteers After Oral Administration
Volume 3, Issue 3, June 2015, Pages: 89-92
Received: Feb. 21, 2015;
Accepted: Mar. 1, 2015;
Published: May 28, 2015
Views 4175 Downloads 118
Bushra Munir, Department of Applied chemistry and Biochemistry, Govt. College University Faisalabad, Faisalabad, Pakistan
Bilal Ahmed, Department of Applied chemistry and Biochemistry, Govt. College University Faisalabad, Faisalabad, Pakistan
Abdul Ghaffar, Department of Applied chemistry and Biochemistry, Govt. College University Faisalabad, Faisalabad, Pakistan
Tahira Iqbal, Department of Applied chemistry and Biochemistry, Govt. College University Faisalabad, Faisalabad, Pakistan
Naila Rafiq, Department of Applied chemistry and Biochemistry, Govt. College University Faisalabad, Faisalabad, Pakistan
Farah Latif, Department of Applied chemistry and Biochemistry, Govt. College University Faisalabad, Faisalabad, Pakistan
Pyrazinamide is use for the treatment of tuberculosis in all over the world. Bio kinetics deals with the mathematical description of drug changes in the body with time function. This study was designed to investigate the bio kinetics of Pyrazinamide after oral administration of Pyrazinamide (25mg) tablet in 10 healthy volunteers. The blood samples of each volunteer were collected from 0.5 to 12 hours at different time intervals after the medication. The concentration of Pyrazinamide in plasma samples were determined by high performance liquid chromatography (HPLC). Quantitative observations were recorded that include the mean ± SD value of absorption rate constant (Ka), time to peak (Tmax) and peak concentration (Cmax) were 0.38 ± 0.25/h, 2.248 ± 0.64 h and 4.165 ± 2.13µg/mL, respectively. The mean ± SD values of absorption half-life (t1/2a) and elimination half-life (t1/2b) were 2.078 ± 1.678h and 0.2908 ± 1.721 hours. The mean ± SD values of volume of distribution and total body clearance were 40 ± 27.4L and 3.351 ± 1.27 h, respectively. Mean residue time (MRT) showed mean ± SD and area under curve (AUC) were 17.23 ± 12.78 h and 90.4 ± 76.2 h.mg/L, respectively.
HPLC Analysis and Bio-kinetics Study of Pyrazinamide in Healthy Volunteers After Oral Administration, Science Research.
Vol. 3, No. 3,
2015, pp. 89-92.
Ahmadi, K. R., M. E. Weale, Z. Y. Xue, N. Soranzo, D. P Yarnall, K. Y. Maruyama, M. Kobayashi, N. W. Wood, N. K. Spurr, D. K. Burns, A. D. Roses, A. M. Saunders and D. B. Goldstein. 2005. A single Nucleotide polymorphism tagging set for human drug metabolism and transport. Nat. Genet; 37: 84-9.
Barns, P. F., D. L. Lakey and W. J. Burman. 2002. Tuberculosis in patients with HIV infection. Infect. Dis. Clin. N. Am; 16 (1):107-126.
Bhutani, H., S. Singh and K. Chakraborti. 2005. Mechanistic Explanation to the catalysis by pyrazinamide and ethambutol of Reaction between rifampicin and isoniazid in anti-TB FDCs. J. Pharm. Biomed. Anal; 39(5):892-9.
Boshoff, H and V. Mizarahi. 2000. Expression of Mycobacterium smegmatis Pyrazinamidase in Mycobacterium tuberculosis Confers Hypersensitivity to Pyrazinamide and Related Amides. J. of Bactoriol; 182(19): 5479-85.
Brindle, R., J. Odhiambo and D. Mitchison. 2001. Serial counts of Mycobacterium Tuberculosis in sputum as surrogate markers of the sterilizing activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis. Pulmonary Medicine 1:2: 2466-2.
Davies A. P., O. J Billington, T. D. McHugh, D. A. Murchison and S. H. Gillispie. 2000. Comparison of phenotypic and genotypic methods for Pyrazinamide susceptibility testing with Mycobacterium Tuberculosis. J. Clin. Microbiol; 38:3686-3688.
Gennaro, M. C., R. Calvino and C. Abrigo. 2001. Ion interaction reagent reversed-phase high performance liquid chromatography determine of anti-tuberculosis drugs and metabolites in biological fluids. J.chromatogr. B. Sci. Appl; 754(2):477-86.
Gurumurthy, P., G. Ramchandran, A. K. H. Kumar, S. Rajjasekaran, C. Padmapriyadarsini. S. Swaminathan, S. Bhagavathy P. Venkatesa L. Sekar A. Mahilmaran, N. Rawi chandranand and P. Paramesh. 2004. Decreased bioavailibility of rifapmsin and other antituberculosis. Drugs in patients with advanced human immunodeficiency virus Disease. Antimicrob agents Chemother; 48(11):4473-5.
Hardman, J. D., L.E. Limbrid and A.G. Gillman. 2001. Goodman and Gillman. The Pharmacological basis of Therapeutics, 10th Edition McGraw-Hill companies, Inc., 1274- 1277.
Krishnamurthy, A., D. Almeida, C. Rodrigues and A. Mehta. 2004. Comparison of Pyrazinamide drug susceptibility of M. tuberculosis by radiometria and enzymatic pyrazinamide assay. I ndian J. Med. Microbiol; 22(3): 166-168.
Lemaitre N., I. Callebaaut, F. Frenois, V. Jarlier and W. Sougakoff. 2001. Study of the Structure –activity relations pyrazinamide (PncA) from Mycobacterium tuberculosis. J. Biochem; 353(3):453-8.
McIlleron, H., P. Wash, A. Burger, J. Norman, P.I. Folb and P. Smith. 2006. Determinations of rifampin, isoniazed, pyrazinamide and ethambutol Pharmacikineticsin a cohort of tiberculosis patients. Antimicrob Agents. Chemother; 50(4):1170-7.
Mehmedagic, A., P. Vertic, S. Menager, C. Tharasse, C. Chabenat, D. Andre, O. Lafont. 2002. Investigation of the effects of the concomitant caffeine Administration on the metabolic disposition of pyrazinamide in rats. Biopharm. Drugs Disposition; 23(5):191-5.
Nishizato, Y., I. Ieiri, H. Suzuki, M. Kimura, K. Kawabata, T.Horata, H. Takane S. Irie, H. Kusuhara, Y. Urasaki, A. Urae. S. Higuchi, K.Otsuboo Y. Sugiyama. 2003. Polymorphism of OATP-C (SLC21A6) and AOT3 (SLC22A8) Genes: consequences for pra-wastatin Pharmacokinetics. Clin. Pharmacol. Ther; 73:554-65.
Perlman, D.C., Y. Segal, S. Rozenkranz, P. M. Rainey , C.A. Peloquin, R.P.Remmel, K. Chirgwin, N. Salomon and R. Hafner. 2004. The Clinical Pharmokinetics of Pyrazinamide in HIV- Infected Persons With tuberculosis. Clin. Infect. Dis; 38:556-564.
Saigal, S., S.R. Ararwal, H.P. Nandeesh and S.K. Sarin. 2001. Safety of an Ofloxacin-based antitubercularreimen for the treatment of Tuberculosis in patients with underlying chronic liver disease: a Preliminary report. J. Gastroenterol. Hepatol; 16(9): 1028-32.
Scorpio A., P. Lindholm-Levy, L. Heifets, R. Gilman, S. Siddiqi, M. Cynamon And Y. Zhang. 1997. Characterization of pncA mutations in Pyrazinamide-resistant Mycobacterium tuberculosis.Antimicrob. Agents. Chemother. 41: 540-543
Sreevatsan, S., X. Pan, Y. Zhang, B. N. Kreiswirth and J. M. Musser. 2004. Mutations- associated with pyrazinamide resistance in pncA of Mycobacterium tuberculosis complete organism. Clin. Infect. Dis: 39(4):488-96.
Van Hest, R., H. Baars, S. Kik, P, van Gerven, M.C. Trompenaars, N. Kalisvaart S. Keizer, M. Borgdorff, M. Mensen and F. Cobelens. 2004. Hepatotoxicity of rifampin-pyrazinamide and isoniazid preventive Therapy and tuberculosis treatment. Thesis, Department of Tuberculosis Control, Munipal Health Service, Rotterdam.
Wada, M 2001. Effectiveness and problems of PZA-containing 6-month regimen For the treatment of new pulmonary tuberculosis patients. Kekkak; 76(1):33-43.
Woo, J., C.L Wong, R. Teoh and K. Chan. 1987. Liquid chromatographic assay For the simultaneous determination of pyrazinamide and rifampicin In serum samples from patients with tuberculosis meningitis. J. Chromatogr; 420(1):73-80.
Zitkova, L., J. Stastna, J. Tousek and J. Viklicky. 1983. Toxicity of Morphazinamide compared with pyrazinamide. Czech. Med; 6:140- 151.
Zhu., M, J. R. Starke, W. J. Burman, P. Steiner, J.J. Stambaugh, D. Ashkin ,A.E. Bulpitt, S. E. Berning and C. A. Peoquin. 2002. Population Pharmacokinetics modeling of pyrazinamide in children and adults With tuberculosis. Pharmacotherapy. 22(6):686-95.