Pharmacokinetics of Ciprofloxacin in Elderly Subjects

The effects of age and gender on the pharmacokinetics of high-dose intravenous ciprofloxacin in a healthy volunteer study were investigated. Plasma ciprofloxacin concentrations were higher in the elderly than in the young, and the pharmacokinetic parameters were not significantly different between the genders. Ciprofloxacin was well tolerated, with the majority of adverse events related to local reactions at the IV site.Ciprofloxacin, the first oral broad-spectrum fluoroquinolone for the treatment of moderate to serious gram-positive and gram-negative infections, was first marketed in the United States in 1987 (4). The currently approved dosage for intravenous ciprofloxacin in the United States is 200 to 400 mg given every 12 h. Recently a higher dosage regimen of 400 mg every 8 h for the treatment of severe respiratory tract infections was investigated (5). This unapproved intravenous ciprofloxacin regimen was shown to be clinically superior to one with imipenem-cilastin, and it demonstrated excellent tolerability (5). The primary objective of this study was to determine the effect of age on the pharmacokinetics of higher-dose intravenous ciprofloxacin by comparing the pharmacokinetic dispositions in elderly (Ͼ65 years of age) and young (18 to 40 years of age) subjects. The effect of gender on the pharmacokinetics of higher-dose intravenous ciprofloxacin was also investigated by comparing the pharmacokinetic profiles of males and females among both the elderly and the young subjects. The tolerability of higher doses of intravenous ciprofloxacin following single dosing and multiple dosing of 400 mg every 8 h in young and elderly subjects was also assessed.Twenty-four healthy subjects participated in the study. They were divided into two groups as follows: 12 young subjects, ages 18 to 40 (six males and six females), and 12 elderly subjects, aged Ͼ65 years (six males and six females). The subjects were judged to be healthy on the basis of the results of a complete physical examination, a medical history, a 12-lead electrocardiogram, laboratory tests (hematology, blood chemistry, and urinalysis), a urine drug screen, a hepatitis screen, and a human immunodeficiency virus screen. Pregnant females were excluded from the study. The protocol was approved by the Human Research Committee, Millard Fillmore Hospital, Buffalo, N.Y. Written informed consent was obtained from the subjects prior to enrollment in this study.Subjects entered the clinic in the morning on day 0 prior to the first dose and remained confined until 24 h after the last dose. On day 0, a 24-h period of urine collection for the determination of creatinine clearance (CL CR ) was started. On day 1, all subjects received a single 400-mg dose (in 200 ml) of intravenous ciprofloxacin infused for 1 h. Blood and urine samples were collected over the next 24 h to assess the singledose pharmacokinetic profile. On day 2, subjects began the multiple-dose regimen consisting of intravenous ciprofloxacin at 400 mg every 8 h. Dosing every 8 h was continued through da...

supporting

confidence: 89%

mentioning

confidence: 98%

Pharmacokinetics of high-dose intravenous ciprofloxacin in young and elderly and in male and female subjects

Shah

Lettieri

Nix

et al. 1995

“…No significant differences were noted between the first dose and steady-state pharmacokinetic parameters, with the exception of an increase in the apparent volume of distribution. The results were consistent with previous studies in healthy and mildly ill elderly subjects undergoing assessment after single doses of oral ciprofloxacin in that the maximum concentration of drug in serum (Cmax) and area under the concentration-time curve (AUC) were increased compared with those of young volunteers receiving the same doses (2,3,5,9,11,15).These studies suggest that the pharmacokinetics of ciprofloxacin are altered in elderly subjects. However, comparative intravenous and oral ciprofloxacin pharmacokinetic parameters during maintenance dose therapy in the elderly have not been evaluated.…”

supporting

confidence: 90%

Steady-state pharmacokinetics of intravenous and oral ciprofloxacin in elderly patients

Hirata

Guay

Awni

et al. 1989

The steady-state pharmacokinetics of ciprofloxacin were evaluated in nine elderly patients with lower respiratory tract infections after an intravenous dosage regimen of 200 mg every 12 h (n = 9) and an oral dosage regimen of 750 mg every 12 h (n = 6). Ciprofloxacin concentrations in serum and urine were measured by high-performance liquid chromatography. The peak concentration in serum, total body clearance (CLs), steady-state volume of distribution (V8,), and terminal elimination half-life after intravenous dosing were 3.5 + 0.8 ,ug/ml, 4.38 ± 1.80 ml/min per kg, 1.6 ± 0.6 liters/kg, and 5.8 ± 2.4 h, respectively. The peak concentration in serum, time to peak concentration in serum, absorption lag time, and absolute bioavailability (F) after oral dosing were 7.6 ± 2.2 ,Lg/ml, 1.9 ± 1.0 h, 0.4 ± 0.5 h, and 77.7 ± 24.2%, respectively. The elevated drug concentrations in serum samples from the elderly after oral dosing, compared with data obtained from younger subjects, appear to be a function of reduced CLs, renal clearance, and V,,. The increased F observed in some patients may be due to the effect of concomitant or proximate administration of tube feedings, medications which may alter gastric motility or acidity, or decreased first-pass metabolism. The results demonstrate that factors related to age and declining renal function, rather than infectious disease state, may be primary in determining alterations in pharmacokinetic parameters in the elderly. In elderly patients with normal renal function for their age, no dosage adjustment for intravenous or oral ciprofloxacin is necessary.Ciprofloxacin, a quinolone carboxylic acid derivative currently marketed in an oral dosage formulation and available as an investigational intravenous preparation, demonstrates in vitro activity against a broad spectrum of aerobic gramnegative and gram-positive bacteria, including strains resistant to aminoglycosides and beta-lactam antibiotics (6). The drug penetrates well into most tissues and is used clinically in the treatment of a variety of infections, including pneumonia (6).The pharmacokinetics of ciprofloxacin have been characterized in adults with normal and impaired renal function after single and multiple dose administration (4,5,8,9,11,13,14,16,20 ance of ciprofloxacin and a decreased apparent volume of distribution of the drug in elderly subjects.In a multiple dose study in elderly patients with serious infections, Guay et al. (12) characterized the pharmacokinetics of oral ciprofloxacin (750 mg every 12 h) during first dose (acutely ill phase) and maintenance dose (convalescentphase) therapy. No significant differences were noted between the first dose and steady-state pharmacokinetic parameters, with the exception of an increase in the apparent volume of distribution. The results were consistent with previous studies in healthy and mildly ill elderly subjects undergoing assessment after single doses of oral ciprofloxacin in that the maximum concentration of drug in serum (Cmax) and area under the concentration-time...

“…As the number of points used went from 2 to 6, the sum of squared residuals went from 5.5 to 1.8 and the coefficient of determination went from 0.993 to 0.999. (16,17,19), but the study designs, analysis, and reporting of the data have been poor to date, and the question begs further study (26).…”

Section: Methodsmentioning

confidence: 99%

Development of a population pharmacokinetic model and optimal sampling strategies for intravenous ciprofloxacin

Forrest

Ballow

Nix

et al. 1993

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