Pharmacokinetics of oral ciprofloxacin, 100 mg single dose, in volunteers and elderly patients

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%

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%

“…Few investigators have compared the disposition of ciprofloxacin in elderly subjects and young volunteers. Ball et al (2) reported significant increases in the peak ciprofloxacin concentration in serum and area under the serum-concentration-versus-time curve in elderly patients with mild urinary tract infections compared with young volunteers after a single 100-mg oral dose. In both groups, the mean terminal elimination half-lives were almost identical.…”

mentioning

confidence: 99%

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...

“…This increase in concentration may be of therapeutic use but may also contribute to intolerance reactions, especially in patients with renal or hepatic insufficiency. In this context also, the higher ciprofloxacin concentrations in serum in elderly patients, which had been reported by Ball et al (2), should be considered.…”

Section: Discussionmentioning

confidence: 71%

“…The pharmacokinetic characteristics of ciprofloxacin, with a terminal half-life of 3.5 to 4 h, allows twice-daily administration by the parenteral or oral route (2,29).…”

mentioning

confidence: 99%

Prospective randomized controlled study of ciprofloxacin versus imipenem-cilastatin in severe clinical infections

Lode

Wiley

Höffken

et al. 1987

In a randomized prospective study, 66 patients with serious bacterial infections-mainly lower respiratory tract infections-were treated with either imipenem plus cilastatin (32 patients) or ciprofloxacin (34 patients); 30 patients in each group were evaluable for efficacy. Substantial underlying disease was present in most of the patients; pathogens isolated prior to treatment (77 isolates) consisted mainly of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and streptococci. Of the etiologic bacteria, 67% were eradicated by ciprofloxacin treatment and 79% by imipenem therapy; however, two patients (6.7%) failed in the ciprofloxacin group, and six patients (20%) did not respond to imipenem treatment (P = 0.25). All patients with therapeutic failures suffered from severe fatal underlying diseases, which had substantial impact on the outcome of treatment. Therapeutic drug monitoring in the ciprofloxacin patients revealed higher concentrations in serum at days 4 and 8 in comparison with day 1 of treatment, indicating that steady-state conditions were reached between days 1 and 4. The total number of side effects was relatively high-eight imipenem patients (25%) and six ciprofloxacin patients (18%) had reactions. Treatment had to be discontinued due to adverse reactions for three ciprofloxacin patients and two imipenem patients. Major side effects in both groups were gastrointestinal and central nervous system-related symptoms. In terms of clinical and bacteriological efficacy and safety, there was no statistical difference between the two groups, and both groups gave good to excellent results for bacterial infections that were difficult to treat.