Pharmacokinetics of Ciprofloxacin in the Elderly

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...

supporting

confidence: 90%

supporting

confidence: 83%

Section: Discussionmentioning

confidence: 81%

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

Hirata

Guay

Awni

et al. 1989

“…For ketoconazole, this CI was chosen because a change in exposure of ketoconazole by as much as 59% when taken with food does not appear to be of clinical relevance since the package insert does not provide guidance for administration with regard to meal (7). For ciprofloxacin, this CI was chosen because no adjustment of ciprofloxacin dose is required for elderly subjects despite an increase in exposure by 48% in the elderly compared to young adults (2). Only descriptive statistics were determined for the T max and T 1/2 values of indinavir, ketoconazole, and ciprofloxacin and for all pharmacokinetic parameters for didanosine.…”

Section: Methodsmentioning

confidence: 99%

Lack of Effect of Simultaneously Administered Didanosine Encapsulated Enteric Bead Formulation (Videx EC) on Oral Absorption of Indinavir, Ketoconazole, or Ciprofloxacin

Damle

Mummaneni

Kaul

et al. 2002

Didanosine formulation that contains a buffer to prevent it from acid-mediated degradation can result in a significant decrease in the oral absorption of certain drugs because of interactions with antacids. An enteric formulation of didanosine is unlikely to cause such drug interactions because it lacks antacids. This study was undertaken to determine whether the enteric bead formulation of didanosine (Videx EC) , 1.08), respectively. All three studies clearly indicated a lack of interaction. The T max and t 1/2 for indinavir, ketoconazole, and ciprofloxacin were similar between treatments. Our results showed that the lack of interaction of didanosine encapsulated enteric bead formulation with indinavir, ketoconazole, and ciprofloxacin indicates that this enteric formulation of didanosine can be concomitantly administered with drugs whose bioavailability is known to be reduced by interaction with antacids.

“…Because renal function and various metabolic clearance mechanisms decrease with age (13), the pharmacokinetics of amifloxacin may be different in the elderly than it is in younger subjects. Indeed, other fluoroquinolone agents, such as ciprofloxacin, ofloxacin, and pefloxacin, have demonstrated remarkable reductions in renal clearance in the elderly compared with clearance in younger volunteers (1,3,10). Furthermore, this change in metabolism may predispose the elderly to the development of adverse drug reactions, a phenomenon already suggested for ofloxacin (9).…”

mentioning

confidence: 99%

Preliminary study of the pharmacokinetics of oral amifloxacin in elderly subjects

Stroshane

Silverman

Sauerschell

et al. 1990

Amifloxacin pharmacokinetics after a single oral dose in healthy elderly subjects were determined. Five males and five females aged 65 to 79 years and having creatinine clearances of 39.3 to 87.2 ml/h per kg of body weight were given a 200-mg amifloxacin caplet following an overnight fast. Mean (standard deviation) pharmacokinetic parameters for amifloxacin were as follows: maximum observed concentration in plasma, 1.13 (0.48) and 1.95 (0.52) ,ug/ml; half-life, 5.37 (0.96) and 4.47 (0.87) h; total plasma clearance (unadjusted for fraction absorbed), 259 (53) and 199 (55) mi/h per kg; renal clearance, 113 (20) and 86 (26) mi/h per kg; Vjprj,/F (V.,,. is volume of distribution; F is fraction absorbed), 2.05 (0.75) and 1.28 (0.39) liter/kg; and amifloxacin excreted in the urine, 42.5% (14.5%) and 42.8% (10.6%) for males and females, respectively. There were no statistically significant differences in pharmacokinetic parameters between sexes that could not be attributed to differences in body weight. Except for a modest 23% reduction in renal clearance and the suggestion of reduced bioavailablity, mean values of pharmacokinetic parameters for elderly male subjects were similar to those previously determined for younger male volunteers. Therefore, a modification in amifloxacin dosage regimen based solely on age may not be necessary. Amifloxacin (Win 49375) is a fluoroquinolone with antibacterial properties (14). In vitro testing has demonstrated a broad range of activity against aerobic gram-negative and some aerobic gram-positive species (5, 11), suggesting potential clinical use.No pharmacokinetic data for this drug exist for the geriatric population, in which infectious illness and antibacterial treatment are relatively common. Because renal function and various metabolic clearance mechanisms decrease with age (13), the pharmacokinetics of amifloxacin may be different in the elderly than it is in younger subjects. Indeed, other fluoroquinolone agents, such as ciprofloxacin, ofloxacin, and pefloxacin, have demonstrated remarkable reductions in renal clearance in the elderly compared with clearance in younger volunteers (1, 3, 10). Furthermore, this change in metabolism may predispose the elderly to the development of adverse drug reactions, a phenomenon already suggested for ofloxacin (9). Before amifloxacin can be used safely in the elderly, pharmacokinetic determinations need to be made and appropriate dose adjustments, if any, need to be recommended. Therefore, the objective of this preliminary study was to determine the pharmacokinetic behavior of a single 200-mg oral dose of amifloxacin to elderly subjects aged 65 years or older. Approximately 10 ml of blood was collected from each subject at 0 h (predose) and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5,6,8,10,12, 16, 18, and 24 h postdose for the purpose of analysis for amifloxacin. Blood was collected in tubes containing potassium oxalate anticoagulant. Plasma was separated and stored at approximately -20°C until analysis. Urine was collected from each subject ov...