INTERPLAY OF VITAMIN B1 AND SELECTED ESSENTIAL AMINO ACIDS ON THE ANTIBACTERIAL ACTIVITY AND PHARMACOKINETICS OF CIPROFLOXACIN IN RABBITS
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Date
2024-01
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SRI VENKATESWARA VETERINARY UNIVERSITY, TIRUPATI - 517 502. (A.P.) INDIA
Abstract
Drug interaction play a significant role in modulating the pharmacological effect
elicited by the drugs in various clinical conditions. Ciprofloxacin, a commonly used
quinolone group of antibacterial agent used widely in livestock species as well as in
human beings due to its broad spectrum of antibacterial activity. Some of the research
findings revealed that vitamin D, Carica papaya alter the kinetic behaviour of
ciprofloxacin. This created an interest to study the kinetic behaviour of ciprofloxacin in
the presence of vitamin B1 (thiamine) and selected essential amino acid phenylalanine.
It is very common that B-complex group of vitamins and dietary supplements with
antioxidant activity are prescribed along with antibacterial agents. Thiamine (vitamin
B1) is one of B-complex group of vitamin with antioxidant activity, plays a crucial role
in energy metabolism, growth, development and functioning of cells. Phenylalanine acts
as precursor for tyrosine, dopa (dihydroxyphenylalanine) and catecholamine. The
conversion of phenylalanine to tyrosine is facilitated by the enzyme phenylalanine
hydroxylase. The sources of phenylalanine include foods like wheat germ, oats, dairy
products, and various meats.
By keeping this in view the present study was designed to determine the
“Interplay of vitamin B1 and selected essential amino acids on the antibacterial activity
and pharmacokinetics of ciprofloxacin in rabbits” by microbiological assay. Minimum
inhibitory concentration (MIC) of ciprofloxacin using MTCC 443 was calculated by
microbroth dilution technique. The MIC end point in the current study was 0.06 µg.mL
1against E.coli MTCC 443.
The pharmacokinetic study was conducted in rabbits following single oral
administration of ciprofloxacin. Rabbits weighing 2-4 kg randomly divided into 5
groups of 6 each. Group I served as control without any treatment. Group II served as
ciprofloxacin control whereas Group III, IV and V rabbits were coadministered with
thiamine (80 mg.kg-1), phenylalanine (48 mg.kg-1), combination of thiamine &
phenylalanine along with ciprofloxacin (40 mg.kg-1) orally. Blood samples were
collected at predetermined time intervals from 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 12 h and
plasma was used for estimation of ciprofloxacin through bioassay.
Results obtained from the experiment revealed that rabbits of Group III, IV & V
showed improved levels of Cmax are 4.74±0.17, 3.00±0.22, 2.18±0.12 µg.mL-1 and AUC
are 20.30±5.19, 10.09±1.48, 12.85±1.34 µg.h.mL-1 respectively when compared to
values of Cmax and AUC are 2.10±0.14 and 5.90±0.81 µg.h.mL-1 in Group II rabbits
respectively. Among the different interventions thiamine coadministered with
ciprofloxacin showed improved antibacterial activity, bioavailability and duration of
action of ciprofloxacin in rabbits. There is no much significant role of combination of
thiamine and phenylalanine (Group V) coadministration with ciprofloxacin when
compared to only thiamine coadministered with ciprofloxacin (Group III) and only
phenylalanine with ciprofloxacin (Group IV) on kinetic behaviour of ciprofloxacin in
rabbits.
PK-PD integration of the present study revealed that Cmax:MIC>8,
AUC:MIC>125 in Group III, IV and V which implies that the coadministration of
vitamin B1 and phenylalanine and their combination improves the antibacterial activity
and reduce the development of resistance at the selected dose of ciprofloxacin.