Pharmacokinetics of ofloxacin in elderly patients and in healthy young subjects

Molinaro, M.; Villani, Paola; Regazzi, Mario; Rondanelli, R; Doveri, Giulio

doi:10.1007/bf02280765

Cited by 15 publications

(5 citation statements)

References 4 publications

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“…Ofloxacin is renally eliminated and clearance of this drug is decreased by aging in humans, with oral clearances in healthy young, healthy elderly and elderly patients with no impairment of renal function of 233, 169 and 83.3 mL/min, respectively (Molinaro et al, 1992;Rademaker et al, 1989). Since the bioavailability of ofloxacin in young subjects is >95% (Lode et al, 1987), the decrease in clearance is thought to be caused by reduced renal clearance.…”

Section: Discussionmentioning

confidence: 99%

“…Similar biexponential declines in diazepam plasma levels have been found after dosing in dogs and monkeys (Curry et al, 1977;Klotz et al, 1976). Ofloxacin is a renally eliminated drug that shows decreased clearance with aging in humans (Molinaro et al, 1992) and is also similarly cleared by the kidney as the unmetabolized form in monkeys and dogs (Okazaki, 1984;Sudo et al, 1984).…”

Section: Introductionmentioning

confidence: 98%

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Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs

et al. 2014

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1. The pharmacokinetics of acetaminophen (marker of gastric emptying), antipyrine (marker of hepatic metabolic activity and total body water), diazepam (lipophilic and highly distributed), diphenhydramine (hepatic blood flow-limited and alpha-1 acid glycoprotein bound) and ofloxacin (renally eliminated) were evaluated in cynomolgus monkeys (3-18 years old) and beagle dogs (2-11 years old) as models in elderly persons. 2. Gastric pH fluctuated with aging in monkeys and dogs. The concentration of alpha-1 acid glycoprotein appeared to be increased by aging. There were no age-related differences in the absorption rates of the drugs under the conditions used in the study. Total body fat increased and water decreased in monkeys, but these parameters did not change in dogs. 3. Hepatic blood flow decreased in both species, but a significant decrease of hepatic clearance was only seen in monkeys. Renal clearance decreased significantly with age in monkeys and showed a tendency to decrease in dogs. 4. Age-related alterations of physiological parameters in monkeys are in agreement with clinical observations in humans, except for the lack of a change in the plasma albumin concentration. Therefore, this study suggests that monkey might be a suitable animal model for prediction of age-related changes in pharmacokinetics in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs

et al. 2014

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“…ings have suggested that the volume of distribution and total body clearance of a number of fluoroquinolones including ofloxacin might be affected by age and/or gender (1,4,6,12,13). For ofloxacin, following multiple 200-mg doses of ofloxacin administered every 12 h, significant accumulation was noted among elderly patients, whereas C max , AUC, and elimination half-life did not increase in younger patients following 7 days of therapy.…”

Section: Discussionmentioning

confidence: 99%

“…The pharmacokinetics of many drugs are altered by age (14) and/or by gender (9). Molinaro et al (6) reported that, compared with healthy young subjects, the elimination of ofloxacin was delayed in elderly patients. The objective of this study was to evaluate the influence of age and gender on the pharmacokinetics of levofloxacin in healthy subjects.…”

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confidence: 99%

Absence of age and gender effects on the pharmacokinetics of a single 500-milligram oral dose of levofloxacin in healthy subjects

Chien¹,

Chow²,

Natarajan³

et al. 1997

Antimicrob Agents Chemother

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The influence of age and gender on the pharmacokinetics of levofloxacin in healthy subjects receiving a single oral 500-mg dose of levofloxacin was investigated in this parallel design study. Six young males (aged 18 to 40 years), six elderly males (aged > or = 65 years), six young females (aged 18 to 40 years), and six elderly females (aged > or = 65 years) were enrolled and completed the study. The study reveals that the bioavailability (rate and extent) of levofloxacin was not affected by either age or gender. In both age (young and elderly) and gender (male and female) groups of subjects, peak concentrations in plasma were reached at approximately 1.5 h after dosing; renal clearance of levofloxacin accounted for approximately 77% of total body clearance, and approximately 76% of the administered dose was recovered unchanged in urine over the 36 h of collection. The apparent differences in the calculated pharmacokinetic parameters for levofloxacin between the age groups (young versus elderly) and between the gender groups (males versus females) could be explained by differences in renal function among the subjects. A single dose of 500 mg of levofloxacin administered orally to both young and old, male and female healthy subjects was found to be safe and well tolerated. As the differences in levofloxacin kinetics between the young and the elderly or the males and the females are limited and are mainly related to the renal function of the subjects, dose adjustment based on age or gender alone is not necessary.

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“…Ofl oxacin and ciprofl oxacin are applied in the treatment of infections outside the urinary tract because they have much lower minimum inhibitory concentrations against sensitive organisms than their predecessors, such as nalidixic acid [1,2] . During the past decade, there has been a growing interest in obtaining adequate information about the effects of fl uoroquinolones in humans [3][4][5][6] as well as in women in comparison with men [7][8][9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Influence of Sex on the Pharmacokinetics of Ciprofloxacin and Ofloxacin

Konieczna¹,

Chmielewska²,

Lamparczyk³

2006

Chemotherapy

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The pharmacokinetics of orally administered ciprofloxacin and ofloxacin were studied in healthy volunteers to assess the influence of sex on drug bioavailability. The first group of subjects (9 males and 9 females) received a single oral dose of 200 mg ofloxacin, and the second group of volunteers included 24 subjects (12 males and 12 females) treated with a single oral dose of 100 mg ciprofloxacin. Blood samples (3 ml) were collected and investigated in this parallel design study in both groups, and ciprofloxacin and ofloxacin concentrations were determined. These experimental data, which had not been changed by any mathematical operation, were collected and used to determine the effect of sex on the pharmacokinetic profile using parametric and non-parametric tests as well as multivariate classification tools like cluster analysis (CA) and principal component analysis (PCA). The following variables demonstrated significant differences (p < 0.05) in c_0.5, c_1.5, c_2.0, c_4.0, c₁₀, c_12.0, c₂₄ and c_6.0, c_8.0, c_10.0 for ofloxacin and ciprofloxacin, respectively, using Student’s t test and ANOVA. Therefore the alternative hypothesis about sex differences between males and females was accepted. The CA and PCA plot separated females from males and allowed to select subjects accounting for differences between males and females. Data on the whole pharmacokinetic profile enabled to determine subtle sex differences between males and females.

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Pharmacokinetics of ofloxacin in elderly patients and in healthy young subjects

Cited by 15 publications

References 4 publications

Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs

Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs

Absence of age and gender effects on the pharmacokinetics of a single 500-milligram oral dose of levofloxacin in healthy subjects

Influence of Sex on the Pharmacokinetics of Ciprofloxacin and Ofloxacin

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