Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits

R. J. Perkins, W. Liu, G. Drusano, A. Madu, M. Mayers, C. Madu, M. H. Miller

Research output: Contribution to journalArticle

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Abstract

The purpose of this study was to evaluate the pharmacokinetics of ofloxacin in serum and vitreous humor samples from albino and pigmented rabbits by using a recently described animal model which permits robust estimation of parameter values. The drug was administered to rabbits intravenously, multiple vitreous humor and serum samples were taken from each rabbit, and the vitreous humor and serum samples were assayed by high- pressure liquid chromatography. The pharmacokinetic parameters were determined with RSTRIP, an iterative, nonlinear, weighted, least-squares regression program. Eight New Zealand White rabbits and eight Dutch belted rabbits (split into single-dose and multiple-dose groups) were investigated in this study. The value of penetration into the vitreous humor of albino rabbits (n = 6) was 32.6% ± 2.12%, with terminal-elimination half-life values of 3.21 and 2.39 h, respectively, for vitreous humor and serum. In pigmented rabbits after a single dose (n = 3) and with a steady-state concentration of drug in serum (n = 4), penetration values were similar, at 30.4% ± 2.98% and 30.0% ± 4.12%, respectively (P > 0.10). Following a single dose of ofloxacin, pigmented animals had elimination half-life values from serum and vitreous humor of 2.64 and 4.32 h, respectively. After steady state was achieved, half-life values for serum and vitreous humor were 3.12 and 6.05 h, respectively. By comparing pigmentation, dose mode, and elimination from vitreous humor, the vitreous humor half-life value for singly dosed albino rabbits (3.21 h) was not more rapid than that for singly dosed pigmented rabbits (4.32 h [P > 0.10]) but was more rapid than that for multiply dosed pigmented rabbits (6.05 h [P < 0.05]). The excellent penetration of ofloxacin into uninflamed rabbit eyes in conjunction with the higher levels in blood found in humans and greater activity against coagulase-negative staphylococci suggest that ofloxacin may be preferable to other quinolones for evaluation in the prophylaxis and treatment of bacterial eudophthalmitis.

Original languageEnglish (US)
Pages (from-to)1493-1498
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume39
Issue number7
StatePublished - 1995
Externally publishedYes

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Vitreous Body
Ofloxacin
Pharmacokinetics
Rabbits
Serum
Half-Life
Coagulase
Quinolones
Pigmentation
Least-Squares Analysis
Staphylococcus
Human Activities
Pharmaceutical Preparations
Animal Models
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Perkins, R. J., Liu, W., Drusano, G., Madu, A., Mayers, M., Madu, C., & Miller, M. H. (1995). Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits. Antimicrobial Agents and Chemotherapy, 39(7), 1493-1498.

Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits. / Perkins, R. J.; Liu, W.; Drusano, G.; Madu, A.; Mayers, M.; Madu, C.; Miller, M. H.

In: Antimicrobial Agents and Chemotherapy, Vol. 39, No. 7, 1995, p. 1493-1498.

Research output: Contribution to journalArticle

Perkins, RJ, Liu, W, Drusano, G, Madu, A, Mayers, M, Madu, C & Miller, MH 1995, 'Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits', Antimicrobial Agents and Chemotherapy, vol. 39, no. 7, pp. 1493-1498.
Perkins RJ, Liu W, Drusano G, Madu A, Mayers M, Madu C et al. Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits. Antimicrobial Agents and Chemotherapy. 1995;39(7):1493-1498.
Perkins, R. J. ; Liu, W. ; Drusano, G. ; Madu, A. ; Mayers, M. ; Madu, C. ; Miller, M. H. / Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits. In: Antimicrobial Agents and Chemotherapy. 1995 ; Vol. 39, No. 7. pp. 1493-1498.
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title = "Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits",
abstract = "The purpose of this study was to evaluate the pharmacokinetics of ofloxacin in serum and vitreous humor samples from albino and pigmented rabbits by using a recently described animal model which permits robust estimation of parameter values. The drug was administered to rabbits intravenously, multiple vitreous humor and serum samples were taken from each rabbit, and the vitreous humor and serum samples were assayed by high- pressure liquid chromatography. The pharmacokinetic parameters were determined with RSTRIP, an iterative, nonlinear, weighted, least-squares regression program. Eight New Zealand White rabbits and eight Dutch belted rabbits (split into single-dose and multiple-dose groups) were investigated in this study. The value of penetration into the vitreous humor of albino rabbits (n = 6) was 32.6{\%} ± 2.12{\%}, with terminal-elimination half-life values of 3.21 and 2.39 h, respectively, for vitreous humor and serum. In pigmented rabbits after a single dose (n = 3) and with a steady-state concentration of drug in serum (n = 4), penetration values were similar, at 30.4{\%} ± 2.98{\%} and 30.0{\%} ± 4.12{\%}, respectively (P > 0.10). Following a single dose of ofloxacin, pigmented animals had elimination half-life values from serum and vitreous humor of 2.64 and 4.32 h, respectively. After steady state was achieved, half-life values for serum and vitreous humor were 3.12 and 6.05 h, respectively. By comparing pigmentation, dose mode, and elimination from vitreous humor, the vitreous humor half-life value for singly dosed albino rabbits (3.21 h) was not more rapid than that for singly dosed pigmented rabbits (4.32 h [P > 0.10]) but was more rapid than that for multiply dosed pigmented rabbits (6.05 h [P < 0.05]). The excellent penetration of ofloxacin into uninflamed rabbit eyes in conjunction with the higher levels in blood found in humans and greater activity against coagulase-negative staphylococci suggest that ofloxacin may be preferable to other quinolones for evaluation in the prophylaxis and treatment of bacterial eudophthalmitis.",
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AU - Liu, W.

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AU - Mayers, M.

AU - Madu, C.

AU - Miller, M. H.

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