Pharmacokinetics of ciprofloxacin after intravenous and increasing oral doses

Abstract

The pharmacokinetics of ciprofloxacin were evaluated after increasing single oral doses of 100, 250, 500 and 1000 mg, and an intravenous dose of 100 mg given to each of 12 healthy volunteers (6 females and 6 males). Concentrations in serum and urine were determined by microbiological assay. The rise in peak serum concentrations and the values of the total area under the serum concentration curve were proportional to the increase in the oral doses. As the oral dose increased a slight increase was observed in the apparent time lag before absorption from 0.34 h after 100 mg to 0.53 h after 1000 mg. The serum half-life after the intravenous dose was 3.2 h. After the oral doses shorter apparent half-life values were observed. The intravenous dose showed an elimination phase distribution volume of 2.76 l/kg and total body clearance of 40.7 l/h. The total urinary excretion was 42.2 +/- 15.6% of the dose after the intravenous dose; the figure was lower after the oral doses. The bioavailability of the 100 mg oral dose was 83.7% as calculated from the value of the total area under the serum curve after the same oral and intravenous dose in all 12 subjects. Ciprofloxacin thus demonstrates normal linear pharmacokinetics, the rise in serum concentrations being proportional to the dose.

Pharmacokinetics of ciprofloxacin after single intravenous and repeat oral administration to cats

“…Serum ciprofloxacin disposition curves after intravenous administration were best fit to an open bicompartmental model in all the animals, which is in accordance with most of the results reported for human beings ( Bergan et al, 1987;Dudley et al, 1987) and domestic animals, such as, dogs (Abadía et al, 1994;Cester et al, 1996), rabbits (Barriere et al, 1987), chickens (Atta & Sharif, 1997;Anadón et al, 2001), ponies (Dowling et al, 1995), sheep (Muñ oz et al, 1996 and goats (García Ovando et al, 2000).…”

“…The application of a microbiological assay for measuring ciprofloxacin concentration is adequate, as there is no report of clinically relevant active metabolites in any animal species. Active ciprofloxacin metabolites in human serum, when analyzed by high-pressure liquid chromatography (HPLC), are present in very low quantities, <10% of ciprofloxacin serum concentration (Wise & Donovan, 1987;Zeiler et al, 1987) and in some cases are not quantifiable (Bergan et al, 1987). Equally, ciprofloxacin metabolites have been detected in calf urine (Nouws et al, 1988) and in chickens plasma and tissue (Anadón et al, 2001), but they exhibited no significant antimicrobial activity.…”

“…Moreover, microbiological assay has been extensively used for ciprofloxacin quantification in human pharmacokinetic studies (González et al, 1984;Tartaglione et al, 1986;Bergan et al, 1987) and also in domestic animals (Siefert et al, 1986;Barriere et al, 1987;Walker et al, 1990;Dowling et al, 1995;Atta & Sharif, 1997). A very good correlation has been reported between this method and HPLC (González et al, 1984;Joos et al, 1985;Bergan et al, 1987). V d(area) , volume of distribution; K a , absorption rate constant; T lag , lag time; t 1/2(a) , absorption halflife; K el , elimination rate constant; T max , time of maximum concentration; C max , maximum concentration; F, bioavailability; C p(avg) , average serum concentration; C p,ss(max) , maximum concentration at steady-state; C p,ss(min) , minimum concentration at steady-state; R A , accumulation index.…”

“…Ciprofloxacin is a second-generation fluoroquinolone widely used and extensively studied in human medicine (González et al, 1984;Drusano et al, 1986a,b;Tartaglione et al, 1986;Bergan et al, 1987;Dudley et al, 1987;Plaisance et al, 1987). In addition, it has been studied in many animal species, such as rats and monkeys (Siefert et al, 1986), rabbits (Barriere et al, 1987), pigs and calves (Nouws et al, 1988;Fang et al, 2000), ponies (Dowling et al, 1995), horses (Yun et al, 1994), chickens (Atta & Sharif, 1997;García Ovando et al, 1999;Anadón et al, 2001), sheep (Muñ oz et al, 1996), goats (García Ovando et al, 2000) and dogs (Walker et al, 1990;Abadía et al, 1994Abadía et al, , 1995.…”

Pharmacokinetics of CIPRODEX® otic in pediatric and adolescent patients

“…This C max was approximately 570-fold lower than the mean C max of 760 ng/mL reported after a therapeutic 250 mg oral dose of ciprofloxacin in adult subjects [16]. The mean ciprofloxacin t 1/2 was approximately 3 h (range 1.8-5.3 h) and is similar to that reported after oral doses in adults [17].…”