24 Journal of Applied Biopharmaceutics and Pharmacokinetics, 2013, 1, 24-30
E-ISSN: 2309-4435/13 © 2013 Pharma Professional Services
Disposition Kinetic of Cloxacillin in Healthy and Nephropathic
Goats with Immunological and Residual Level in Blood and
Tissues
Sanjib Khargharia
1,*
, Animesh K. Chakraborty
1
, Anjan Bhattacharyya
2
and
Tapan K. Mandal
1
1
Department of Pharmacology & Toxicology, West-Bengal University of Animal and Fishery Sciences,
Mohanpur, Nadia-741252, West-Bengal, India
2
Department of Agricultural Chemicals, Bidhan Chandra KrishiViswavidyalaya, Mohanpur, Nadia-741252,
West-Bengal, India
Abstract: In the present investigation, we evaluated the efficacy of pharmacokinetic profile in healthy as well as
nephropathic black-Bengal goats (n=6) of either sex through single intravenous route along with metabolism aspects in
all vital organs as well as urine. Nephropathic goats resulted higher B (41.03 ± 3.87 gmL
-1
), t1/2 (1.17 ± 0.06hr) and low
(0.59 ± 0.03 hr
-1
) and ClB (25.70 ± 2.86 mlh
-1
kg
-1
) compared to healthy goats. Continuous administration via
intramuscular route up to 60 days revealed biochemical, hematological, histopatholocial changes in therapeutic (TP) as
well as below therapeutic dosage (HTP) level in black-Bengal goats. Present study also revealed immunosuppressive
effect during 60 days continuous intramuscular administration and confirmed stimulatory effect on hepatic microsomal
enzyme system.
Keywords: Cloxacillin, pharmacokinetic, hematological, biochemical, immunological studies.
INTRODUCTION
Antibiotic treatment of patients remains a significant
challenge for all nations with persisting high mortality
and morbidity rates. The importance of effective
therapy continues to grow with increasing numbers of
patients with increasing levels of sickness. Compelling
evidence suggests that in patients, source control of
the pathogen is appropriate antibiotic therapy which
remains the most important intervention that the
clinician can implement at early. Therefore, optimizing
antibiotic therapy should be a priority in the
management for patients. Some of these antibiotics are
encountered by the organism over long period of time.
Continuous low level exposure to such antibiotics may
increase the susceptibility of the host to various
diseases due to immunity breakdown. It has therefore,
become important to screen antibiotic at therapeutic
dose level with respect to their immunotoxic,
biochemical and hematological potential. Cloxacillin,
semi synthetic amino penicillin which has activity
against penicillin-sensitive gram positive as well as
some gram negative bacteria continues to be a useful
antimicrobial drug for its low index of toxicity and
reliable absorption which continues to make it an
attractive agent in the treatment of variety of infections.
Pharmacokinetic is concerned with study and
*Address correspondence to this author at the MNPC, University of Iowa, Iowa
City, IA-52246, USA; Mobile: 3194008179;
E-mail: sanjibkharghoria@yahoo.com
characterization of time course of drug absorption,
distribution, metabolism and excretion [1]. Disease
states alter the pharmacokinetic parameters of many
drugs. It has been reported that the kinetic behavior of
many drugs were altered following administration by
different routes in experimentally induced diseased
models of goats and dogs [2-4]. The routine use of
conventional dosage regimen in patients suffering from
liver and/or renal diseases may result in excessive
accumulation of drug in the body and consequently
may expose the patient to an excessive risk of serious
side effects and toxicity.
So in the present investigation, we evaluated
disposition kinetics of cloxacillin after single
intravenous (IV) administration in healthy as well as
nephropathic black-Bengal goats. Accumulation of this
antibiotic after long term exposure in vital organs and
urine were evaluated after repeated therapeutic (TP)
and one half of therapeutic dose (HTP) consecutively
for 60 days through intramuscular (IM) administration
and investigated its role in blood biochemistry and liver
cytochrome P
450
component to screen for immunotoxic,
biochemical and hematological potential.
MATERIALS AND METHODS
Materials
Cloxacillin was obtained as gift from M/S Alembic
Ltd, Mumbai, India. The purity of the compound was
98%.