J Vet Sci.  2007 Dec;8(4):357-360. 10.4142/jvs.2007.8.4.357.

Disposition kinetics and dosage regimen of levofloxacin on concomitant administration with paracetamol in crossbred calves

• Dumka VK

• KMID: 1106215
• DOI: http://doi.org/10.4142/jvs.2007.8.4.357

Abstract

The disposition kinetics of levofloxacin was investigated in six male crossbred calves following single intravenous administration, at a dose of 4 mg/kg body weight, into the jugular vein subsequent to a single intramuscular injection of paracetamol (50 mg/kg). At 1 min after the injection of levofloxacin, the concentration of levofloxacin in plasma was 17.2 +/- 0.36 microgram/ml, which rapidly declined to 6.39 +/- 0.16 microgram/ml at 10 min. The drug level above the MIC90 in plasma, was detected for up to 10 h. Levofloxacin was rapidly distributed from blood to the tissue compartment as evidenced by the high values of the distribution coefficient, alpha (17.3 +/- 1.65 /h) and the ratio of K12/K21 (1.83 +/- 0.12). The values of AUC and Vdarea were 12.7 +/- 0.12 microgram.h/ml and 0.63 +/- 0.01 l/kg. The high ratio of the AUC/MIC (126.9 +/- 1.18) obtained in this study indicated the excellent antibacterial activity of levofloxacin in calves. The elimination half-life, MRT and total body clearance were 1.38 +/- 0.01 h, 1.88 +/- 0.01 h and 0.32 +/- 0.003 l/kg/h, respectively. Based on the pharmacokinetic parameters, an appropriate intravenous dosage regimen for levofloxacin would be 5 mg/kg repeated at 24 h intervals when prescribed with paracetamol in calves.

Keyword

calves; disposition; dosage; levofloxacin; paracetamol

MeSH Terms

Acetaminophen/administration & dosage/*pharmacokinetics
Animals
Anti-Bacterial Agents/administration & dosage/blood/*pharmacokinetics
Area Under Curve
Cattle/*metabolism
Drug Therapy, Combination
Half-Life
Hybridization, Genetic
Injections, Intravenous/veterinary
Male
Ofloxacin/administration & dosage/blood/*pharmacokinetics
Time Factors

Figure

• 

  Fig. 1 Semilogarithmic plot of the plasma concentration-time profile of levofloxacin following a single intravenous injection of 4 mg/kg body weight subsequent to a single intramuscular injection of paracetamol (50 mg/kg) in crossbred calves. Values are presented as mean ± SE of six animals. The data was analyzed according to the two-compartment open model. Distribution (α) and elimination (β) phases are represented by least square regression lines. The calculated points (o) of the distribution phases were obtained by the feathering technique.

Reference

1. Ahanger AA, Srivastava AK, Raina R. Disposition kinetics of enrofloxacin in crossbred calves. J Vet Pharmacol Toxicol. 2003. 3:16–20.

2. Aliabadi FS, Lees P. Pharmacokinetics and pharmacodynamics of danofloxacin in serum and tissue fluids of goats following intravenous and intramuscular administration. Am J Vet Res. 2001. 62:1979–1989.

3. Aliabadi FS, Ali BH, Landoni MF, Lees P. Pharmacokinetics and PK-PD modeling of danofloxacin in camel serum and tissue cage fluids. Vet J. 2003. 165:104–118.

4. Aliabadi FS, Landoni MF, Lees P. Pharmacokinetics (PK), pharmacodynamics (PD) and PK-PD integration of danofloxacin in sheep biological fluids. Antimicrob Agents Chemother. 2003. 47:626–635.

5. Apley MD, Upson DW. Lung tissue concentrations and plasma pharmacokinetics of danofloxacin in calves with acute pneumonia. Am J Vet Res. 1993. 54:937–943.

6. Arret B, Johnson DP, Kirshbaum A. Outline of details for microbiological assays of antibiotics: second revision. J Pharm Sci. 1971. 60:1689–1694.

7. Atef M, El-Gendi AY, Aziza , Amer MM, Abd El-Aty AM. Some pharmacokinetic data for danofloxacin in healthy goats. Vet Res Commun. 2001. 25:367–377.

8. Bakken JS. The fluoroquinolones: how long will their utility last? Scand J Infect Dis. 2004. 36:85–92.

9. Chulavatnatol S, Chindavijak B, Vibhagool A, Wananukul W, Sriapha C, Sirisangtragul C. Pharmacokinetics of levofloxacin in healthy Thai male volunteers. J Med Assoc Thai. 1999. 82:1127–1135.

10. Davis R, Bryson HM. Levofloxacin. A review of its anti-bacterial activity, pharmacokinetics and therapeutic efficacy. Drugs. 1994. 47:677–700.

11. Destache CJ, Pakiz CB, Larsen C, Owens H, Dash AK. Cerebrospinal fluid penetration and pharmacokinetics of levofloxacin in an experimental rabbit meningitis model. J Antimicrob Chemother. 2001. 47:611–615.

12. Dumka VK, Srivastava AK. Pharmacokinetics, urinary excretion and dosage regimen of levofloxacin following single intramuscular administration in cross bred calves. J Vet Sci. 2006. 7:333–337.

13. Dumka VK, Srivastava AK. Disposition kinetics, urinary excretion and dosage regimen of levofloxacin formulation following single intravenous administration in crossbred calves. Vet Res Commun. 2007. 31:873–879.

14. Edelstein PH, Edelstein MA, Lehr KH, Ren J. In-vitro activity of levofloxacin against clinical isolates of Legionella spp, its pharmacokinetics in guinea pigs, and use in experimental Legionella pneumophila pneumonia. J Antimicrob Chemother. 1996. 37:117–126.

15. Gibaldi M, Perrier D. Gibaldi M, Perrier D, editors. Method of residuals. Pharmacokinetics. 1982. 2nd ed. New York: Marcel Dekker;433–444.

16. Gips M, Soback S. Norfloxacin nicotinate pharmacokinetics in unweaned and weaned calves. J Vet Pharmacol Ther. 1996. 19:130–134.

17. Ito T, Yano I, Masuda S, Hashimoto Y, Inui K. Distribution characteristics of levofloxacin and grepafloxacin in rat kidney. Pharm Res. 1999. 16:534–539.

18. Kaartinen L, Salonen M, Alli L, Pyörälä S. Pharmacokinetics of enrofloxacin after single intravenous, intramuscular and subcutaneous injections in lactating cows. J Vet Pharmacol Ther. 1995. 18:357–362.

19. Klesel N, Geweniger KH, Koletzki P, Isert D, Limbert M, Markus A, Riess G, Schramm H, Iyer P. Chemotherapeutic activity of levofloxacin (HR 355, DR-3355) against systemic and localized infections in laboratory animals. J Antimicrob Chemother. 1995. 35:805–819.

20. Langtry HD, Lamb HM. Levofloxacin. Its use in infections of the respiratory tract, skin, soft tissues and urinary tract. Drugs. 1998. 56:487–515.

21. McKellar QA, Sanchez Bruni SF, Jones DG. Pharmacokinetic/pharmacodynamic relationship of antimicrobial drugs used in veterinary medicine. J Vet Pharmacol Ther. 2004. 27:503–514.

22. North DS, Fish DN, Redington JJ. Levofloxacin, a second-generation fluoroquinolone. Pharmacotherapy. 1998. 18:915–935.