Biomedical subjects

E Radwanski

Publications and source records attributed to E Radwanski.

60 records · Page 4Linked to original sources

PubMedDate not supplied

Comparative bioavailability of ceftibuten in capsule and suspension forms.

The comparative bioavailability of ceftibuten, a new third-generation cephalosporin antibiotic given orally once daily, in capsule and suspension dosage forms, was assessed in healthy male subjects. In three separate studies, subjects received either a 400-mg dose as a suspension or one laboratory-batch, 400-mg capsule; one laboratory-batch, 400-mg capsule or two laboratory-batch, 200-mg capsules; or one production-batch, 400-mg capsule or two laboratory-batch, 200-mg capsules. Plasma samples were assayed for ceftibuten using high-performance liquid chromatography, and the data were assessed using pharmacokinetic and statistical methods. Confidence intervals for the maximum plasma concentration and the area under the plasma concentration-time curve extrapolated to infinity were within 80% to 125% of guidelines, demonstrating the bioequivalence of the two treatments within each of the three studies. One 400-mg capsule (laboratory or production batch) was bioequivalent to two 200-mg capsules used in a clinical efficacy trial; the 400-mg suspension was bioequivalent to a 400-mg capsule (laboratory batch). Thus we concluded that the capsule and the suspension dosage forms were bioequivalent.

Administration, Oral↗

PubMedDate not supplied

Pharmacokinetics of loratadine and pseudoephedrine following single and multiple doses of once- versus twice-daily combination tablet formulations in healthy adult males.

The pharmacokinetic profiles of single and multiple doses of loratadine, descarboethoxyloratadine (DCL) (the major active metabolite of loratadine), and pseudoephedrine were determined in a randomized, open-label, two-way crossover study in 24 healthy men. Subjects received a single dose (day 1) and multiple doses (days 3 to 10) of a once-daily (QD) formulation of loratadine 10 mg in an immediate-release coating and pseudoephedrine sulfate 240 mg in an extended-release core (CLAR-ITIN-D 24 HOUR tablets), and a twice-daily (BID) formulation of loratadine 5 mg in an immediate-release coating and pseudoephedrine sulfate 120 mg, with 60 mg in an immediate-release coating and 60 mg in the barrier-protected core (CLARITIN-D 12 HOUR tablets) in study sessions, each separated by a 10-day washout period. Both regimens were safe and well tolerated. On day 1, plasma loratadine, DCL, and pseudoephedrine concentrations were higher following the QD formulation than following the BID formulation, as expected. On day 10, loratadine and DCL maximum plasma concentration (Cmax) values were, on average, 87% and 35% higher, respectively, for the QD formulation than for the BID formulation; however, the values of the area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) for loratadine and DCL were equivalent (90% confidence interval [CI]: 83% to 110% for loratadine; 90% to 107% for DCL). On day 10, pseudoephedrine Cmax and AUC0-24 values were equivalent (90% CI for Cmax: 94% to 109%; for AUC: 91% to 106%) for the two formulations, and lower pseudoephedrine concentrations were observed from 16 to 24 hours with the QD formulation. Both loratadine/pseudoephedrine formulations produced equivalent loratadine and DCL AUC0-24 values and equivalent pseudoephedrine Cmax and AUC0-24 values following multiple dosing. The lower pseudoephedrine concentrations in the evening with the QD formulation may minimize the potential for insomnia in patients when compared with the BID formulation.

Adult↗

PubMedDate not supplied

Pharmacokinetics of intramuscularly administered isepamicin in man.

The pharmacokinetics of isepamicin, a broad-spectrum aminoglycoside antibiotic, was studied in man after intramuscular administration. Two groups each of 6 volunteers received isepamicin for 10 consecutive days by intramuscular injection at respective doses of 7.5 mg/kg once daily or 7.5 mg/kg twice daily. Plasma and urinary concentrations of isepamicin were determined using a specific HPLC method. In both groups, there was no drug accumulation following multiple administration. The t1/2, which ranged from 2.4 to 2.7 h, was independent of the dosage regimen. Isepamicin excreted into (0-24 h) urine accounted for virtually 100% of the dose. The results show that the pharmacokinetics of isepamicin are similar with these dosage regimens. The drug undergoes no detectable biotransformation, does not accumulate upon multiple dosing, and is cleared solely by urinary excretion.

Adolescent↗

PubMedDate not supplied

Renal changes associated with naproxen sodium administration in cynomolgus monkeys.

Naproxen sodium was administered to cynomolgus monkeys (Macaca fascicularis) by oral gavage at daily doses of 44, 88, or 176 mg/kg for 2 wk (2 monkeys/gender) or of 44 mg/kg for 13 wk (4 monkeys/gender). Body weight loss occurred in at least one monkey in all naproxen sodium-dosed groups in the 2-wk (up to 16% loss) and 13-wk (up to 22% loss) studies. Increases in plasma naproxen concentrations were dose proportional between 44 and 88 mg/kg but were less than dose proportional between 88 and 176 mg/kg. Up to 2-fold increases in creatinine and/or serum urea nitrogen values as well as higher renal weights occurred in monkeys receiving 176 mg/kg for 2 wk or 44 mg/kg for 13 wk. Microscopically, renal changes were observed in all naproxen sodium-dosed groups. Renal findings after 2 wk of exposure included increased interstitial ground substance, tubular dilatation, and tubulointerstitial nephritis; in the 13-wk study, cortical tubular atrophy and interstitial fibrosis were also observed. These studies identify the kidney as the target organ of naproxen sodium in cynomolgus monkeys.

Animals↗

PubMedDate not supplied

The pharmacokinetics of loratadine in normal geriatric volunteers.

The pharmacokinetics of loratadine, a non-sedating anti-histamine, were studied in 12 normal geriatric volunteers. In an open label fashion, each volunteer received one 40 mg loratadine capsule. Blood was collected prior to and at specified times (up to 120 h) after dosing. Plasma loratadine concentrations were determined by a specific radioimmunoassay and those of an active metabolite, descarboethoxyloratadine, by high performance liquid chromatography. Concentrations of loratadine in the disposition phase were fitted to a biexponential equation and those of descarboethoxyloratadine to either a monoexponential or biexponential equation for pharmacokinetic analysis. Loratadine was rapidly absorbed, reaching a maximum plasma concentration of 50.5 ng/ml at 1.5 h after dosing. The disposition half-lives of loratadine in the distribution and elimination phases were 1.5 and 18.2 h, respectively. The area under the plasma concentration-time curve, was 146.7 h.ng/ml. Descarboethoxyloratadine had a maximum plasma concentration of 28.0 ng/ml at 2.9 h post-dose and an area under the concentration-time curve of 394.9 h.ng/ml. Its disposition half-lives in the distribution and elimination phases were 2.8 and 17.4 h, respectively. Comparison of these data with those from a previous study of loratadine in young adults showed no clear differences in the disposition half-lives between the two groups. The clearance of loratadine tends to be lower in the elderly, but inter-individual variation within each age group appears greater than any age effect.

Age Factors↗

PubMedDate not supplied

Interleukin-10 pharmacokinetics in intact and nephrectomized mice.

The influence of kidney function on interleukin-10 (IL-10) pharmacokinetics was assessed by comparing the disappearance of IL-10 from the circulation in the intact and acutely nephrectomized mice over 1 h following a single bolus injection of E. coli-derived recombinant h IL-10 at 250 micrograms/kg i.v. The intact mice demonstrated a C(max) of 1,172 ng/ml and an AUC(tf) of 385 n g.h/ml. By comparison, there was a 4-fold elevation in C(max) and a 7-fold increase in AUC(tf) in the anephric mice. The serum IL-10 concentration at 1 h post-injection was 87 ng/ml in the intact vs 1,684 ng/ml in the anephric mice. The results imply that IL-10, in common with other cytokines, is eliminated through the kidney.

Animals↗