J Vet Sci.  2006 Dec;7(4):333-337. 10.4142/jvs.2006.7.4.333.

Pharmacokinetics, urinary excretion and dosage regimen of levofloxacin following a single intramuscular administration in cross bred calves

• Dumka VK
• Srivastava AK

• KMID: 1089479
• DOI: http://doi.org/10.4142/jvs.2006.7.4.333

Abstract

The pharmacokinetics and urinary excretion following single intramuscular administration of levofloxacin at a dose of 4 mg/kg was investigated in seven male cross bred calves. Appreciable plasma concentration of levofloxacin (0.38 +/- 0.06 microgram/ml) was detected at 1 min after injection and the peak plasma level of 3.07 +/- 0.08 microgram/ml was observed at 1 h. The drug level above MIC(90) in plasma was detected up to 12 h after administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.14 +/- 0.24 /h). The overall systemic bioavailability of levofloxacin, after intramuscular administration, was 56.6 +/- 12.4%. The high value of AUC (7.66 +/- 0.72 mg.h/ml) reflected the vast area of body covered by drug concentration. Extensive distribution of the drug into various body fluids and tissues was noted by the high value of Vd(area) (1.02 +/- 0.05 l/kg). The high ratio of AUC/MIC (76.6 +/- 7.25) obtained in this study indicated excellent clinical and bacteriological efficacy of levofloxacin in calves. The elimination half-life and MRT were 3.67 +/- 0.4 h and 5.57 +/- 0.51 h, respectively. The total body clearance (Cl(B)) was 204.9 +/- 22.6 ml/kg/h. On the basis of the pharmacokinetic parameters, a suitable intramuscular dosage regimen for levofloxacin in calves would be 1.5 mg/kg repeated at 12 h intervals.

Keyword

calves; dosage; levofloxacin; pharmacokinetics; urinary excretion

MeSH Terms

Animals
Anti-Bacterial Agents/administration & dosage/blood/*pharmacokinetics/urine
Area Under Curve
Biological Availability
Cattle/*metabolism/urine
Half-Life
Injections, Intramuscular/veterinary
Male
Ofloxacin/administration & dosage/blood/*pharmacokinetics/urine

Figure

• 

  Fig. 1 Standard curve of levofloxacin in plasma of cross bred calves. Each point represents the mean of the results from 14 assays.

• 

  Fig. 2 Semilogarithmic plot of plasma concentration-time profile of levofloxacin following its single intramuscular injection of 4 mg/kg b.w. in cross bred calves. Values are presented as mean ± SE (n = 7). The data were analyzed according to the onecompartment open model. Absorption and elimination phases are represented by least square regression lines. The calculated points (o) of distribution phases were obtained by residual technique. Constants A' and B are zero-time intercepts of absorption and elimination phases, respectively.

• 

  Fig. 3 Concentration and cumulative per cent of total dose of levofloxacin excreted in urine of cross bred calves following its single intravenous dose of 4 mg/kg b.w. Each point and bar represents the mean ± SE (n = 7).

Reference

1. 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.

2. 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.

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

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

5. Baggot JD. Principles of Drug Disposition in Domestic Animals. 1977. Philadelphia: Saunders;190–218.

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

7. 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.

8. Davis R, Bryson HM. Levofloxacin. A review of its antibacterial activity, pharmacokinetics and therapeutic efficacy. Drugs. 1994. 47:677–700.

9. 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.

10. Gibaldi M, Perrier D. Pharmacokinetics. 1982. 2nd ed. New York: Marcel Dekker;433–444.

11. Giles CJ, Magonigle RA, Grimshaw WTR, Tanner AC, Risk JE, Lynch MJ, Rice JR. Clinical pharmacokinetics of parenterally administered danofloxacin in cattle. J Vet Pharmacol Ther. 1991. 14:400–410.

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

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

14. 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.

15. Kunin CM, Dornbush AC, Finland M. Distribution and excretion of four tetracycline analogues in normal young men. J Clin Invest. 1959. 38:1950–1963.

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

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

18. Schneider M, Valle M, Woehrle F, Boisrame B. Pharmacokinetics of marbofloxacin in lactating cows after repeated intramuscular administrations and pharmacodynamics against mastitis isolated strains. J Dairy Sci. 2004. 87:202–211.

19. Shem-Tov M, Ziv G, Glickman A, Saran A. Pharmacokinetics and penetration of marbofloxacin from blood into the milk of cows and ewes. Zentralbl Veterinarmed A. 1997. 44:511–519.

20. Shojaee Aliabadi F, 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.

21. Singh K, Srivastava AK. Plasma levels, pharmacokinetics, urinary excretion and dosage regimen of ciprofloxacin in cross bred cow calves. J Punjab Acad Sci. 2000. 2:105–107.

22. TerHune TN, Skogerboe TL, Shostorm VK, Weigel DJ. Comparison of pharmacokinetics of danofloxacin and enrofloxacin in calves challenged with Mannheimia haemolytica. Am J Vet Res. 2005. 66:342–349.