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

Abstract

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...

Crossover assessment of serum bactericidal activity and pharmacokinetics of ciprofloxacin alone and in combination in healthy elderly volunteers

“…The pharmacokinetics of ciprofloxacin in elderly individuals have been reported previously (6,13,16). The somewhat lower mean peak concentration in serum, elimination half-life, and AUC in our subjects probably are explained by their somewhat younger age, better renal function, and generally better state of health than those of the elderly hospitalized or institutionalized individuals studied previously (6, 13, 16).…”

Population pharmacokinetics of marbofloxacin in horses: preliminary analysis

“…, 1998). Decreased systemic clearance of drugs has been associated with inhibition of hepatic metabolism during the acute phase of inflammation (Monshouwer & Witkamp, 2000) and impaired hepatic or renal function (Baggot, 1980; Hirata et al. , 1989).…”

Antimicrobial Therapy for the Elderly Patient

“…The pharmacokinetics of quinolones in aging persons, primarily ciprofloxacin but also enoxacin, ofloxacin, and pefloxacin, have been studied extensively 204–214 ; tissue penetration of these drugs in elderly patients has also been studied 215–217 . These numerous reports can be summarized, although the reported results do not always agree.…”