Weibull function C = Bts-1exp(-lambda ts) was used to describe plasma concentration-time data of ribavirin in 6 healthy subjects following an i.v. dose of 600 mg. A good fit was found in each of the subjects, where the coefficients of determination r2 were > 0.99. The parameters estimated were as follows: B, 5.90 +/- 1.86 micrograms.h1-s; lambda, 0.607 +/- 0.156 h-s; and s, 0.339 +/- 0.085, respectively. The results were compared with those by triexponential function. By providing lower values of AIC and SD, as well as higher values of r2, the Weibull function proved to be superior to triexponential function for data of 3 subjects. These results indicated that both Weibull function and triexponential function provided a good fit of plasma concentration-time data of ribavirin in man following an i.v. dose.

Adult↗

PubMedDate not supplied

Cefixime absorption kinetics after oral administration to humans.

Cefixime (CFX) absorption kinetics after oral administration to humans was studied. Four distinct models, incorporating a delay of absorption and first-order elimination kinetics, i.e. first-order absorption (M1), zero-order absorption (M0), Michaelis-Menten type absorption (MM) and Michaelis-Menten type absorption with 'an absorption window' (MM-delta t) were used to fit concentration data of CFX in 10 Chinese men following an oral dose of 400 mg. r2 and AIC were selected as measures of goodness-of-fit. The results show that the MM-delta t model provided a better fit than the other three models. The kinetic parameters were estimated as follows: Vmax' = 10.80 +/- 3.80 mg.l-1.h-1; K(m)' = 88.31 +/- 2.75 micrograms.ml-1; delta t = 4.75 +/- 0.85 h; T1/2 = 4.20 +/- 0.92 h; Tmax = 5.20 +/- 0.92 h; and Cmax = 6.04 +/- 1.70 mg.l-1.

Absorption↗

PubMedDate not supplied

A double-site absorption model fits to pharmacokinetic data of repaglinide in man.

The plasma concentrations of repaglinide in 16 male subjects were determined after an oral dose of 4 mg. Two-peak concentrations in plasma were observed. A type of one-compartment model with double sites of drug absorption was developed and successfully used to fit the data. A good agreement between observed and predicted data was found in all subjects with correlation index r2 > 0.97. The corresponding pharmacokinetic parameters were estimated as follows: Tmax1 0.61 +/- 0.14 h, Tmax2 1.45 +/- 0.43 h, Cmax1 40.60 +/- 20.57 ng/ml, Cmax2 42.70 +/- 17.54 ng/ml, T1 0.12 +/- 0.07 h, T2 0.67 +/- 0.30 h and T3 1.03 +/- 0.35 h.

Absorption↗

PubMedDate not supplied

Gender difference in ranolazine pharmacokinetics in rats.

Pharmacokinetics of ranolazine (RAN) in both female and male rats was studied. RAN concentrations in plasma were determined after oral administration of 12.5, 25 and 50 mg/kg RAN. Concentrations in tissues, recoveries of RAN in urine and bile were also analyzed following oral dose of 25 mg/kg. It was found that plasma concentrations of RAN in female rats were significantly higher than those in male rats. Drug exposures based on Cmax and AUC in female rats were roughly 2-to 3-fold of those in male rats. Terminate half-life T1/2 and MRT in male rats were shorter than those in female rats. The recoveries in urine and bile of female rats were also markedly higher than those in male rats'. Tissue concentrations of RAN in female rats were also markedly higher than those in male rats. These results demonstrated existence of marked gender difference in RAN pharmacokinetics in rats.

Acetanilides↗

PubMedDate not supplied

Gender differences in limonin pharmacokinetics in rats.

In the present study, the pharmacokinetics of limonin (LM) were investigated in male and female rats. LM concentrations in the plasma were determined after the oral administration of 36 mg/kg LM or after intravenous (i.v.) injection of LM 3.6 mg/kg respectively. Concentrations in the tissues, urine, feces and bile were also analyzed following the oral administration of 36 mg/kg of the test product. It was found that the plasma concentrations of LM in female rats were significantly higher (P < 0.01) than those in male rats. Assessment of the effects of limonin based on the C(max) and AUC in female rats showed that levels were about 50-fold higher than those in male rats after oral administration of 36 mg/kg LM. Furthermore, after i.v. administration of 3.6 mg/kg LM, the C(max) and AUC in female rats was found to be about 3-fold higher than those in male rats. The total excretion of LM in the urine and bile of female rats was also found to be significantly higher than in male rats, which displayed lower concentrations of LM in the tissues, amounting to around one-half to one-tenth of those in female rats, apart from levels in the rectum and duodenum. In conclusion, the present results demonstrate the existence of marked gender difference in LM pharmacokinetics in rats.

Administration, Oral↗

PubMedDate not supplied

Correlation between quinolone uptakes by BCECs in vitro and brain-to-plasma concentration ratios in rats.

Transport of 11 quinolones at the blood-brain barrier (BBB) was studied in vitro by using primarily cultured rat brain capillary endothelial cells (BCECs) and in vivo brain-to-plasma concentration ratios. In vitro, when cells reached confluence, a time course of quinolone uptake was recorded by incubation with a medium contraining quinolones 20 microg/ml at 37 degrees C. A simple two-compartment model was used for fitting the uptake time course and corresponding uptake parameters were estimated. In vivo rats were anesthetized, after in 10 mg/kg of quinoloes followed by infusion of 4 mg/kg/h for 2 hours, the drug concentrations in plasma and brain were measure and brain-to-plasma concentration ratios were calculated. Result showed that sparfloxacin and prulifloxacin have higher uptakes by BCECs and brain-to-plasma concentration ratios, compared with other quinolones, which indicated that the two drugs more easily penetrate into BBB. A good correlation between uptakes by BCECs and brain-to-plasma concentration ratios was found. These results demonstrated uptakes by BCECs in vitro might give prediction of brain-to-plasma ratio for quinolones.

Animals↗

PubMedDate not supplied

Effect of P-glycoprotein inhibitors erythromycin and cyclosporin A on brain pharmacokinetics of nimodipine in rats.

Effect of P-glycoprotein (P-gp) inhibitors erythromycin (Ery) and cyclosporin A(CsA) on brain pharmacokinetics of nimodipine (NMD) in rats was studied. NMD concentrations in rat plasma and brain were determined after iv 2 mg/kg NMD alone, co-administration with Ery and CsA, respectively. It was found that concentrations of NMD in plasma of the three groups had a little difference, but brain concentrations of NMD in rats co-administrated with Ery and CsA were significantly higher than those in rats NMD alone. Significances of NMD in rat brain were found at 20, 40, 60 and 90 min after iv NMD. The brain T(1/2) in rat treated with ery(75.0 min) and CsA(79.0 min) were larger than that (44.2 min) in rats NMD alone. The results indicated that P-gp inhibitors Ery and CsA may increase concentration in rat brain by inhibiting elimination of NMD from brain.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMedDate not supplied

Different effect of erythromycin on absorption kinetics of nimodipine in male and female rats.

Effect of erythromycin (ERY) on oral absorption of nimodipine (NMD) in female and male rat was investigated in vivo and in vitro. In vivo, at 15 min following oral dose of 50 mg/kg ERY, an oral dose 20 mg/kg NMD was given to rats, plasma concentrations of NMD were determined. In vitro, everted jejunum sac and ileum sac were used, NMD transport from mucosal side to serol side was measured, in absences of ERY and cyclosprin A (CSA) or in presence of ERY and CSA. Large gender difference was found after oral dose NDM. Male rats had lower plasma concentration than female rat did. AUC180 and Cmax in male rats were less than 5-folds and 3-folds than those in female rats, respectively. Co-administrating ERY may increase plasma concentrations of NMD in rats. AUC180 in male rats and female rats were 2.2-folds and 1.9-folds of those NMD alone, respectively. Cmax was about 3-folds of that NMD alone. The NMD transport in intestine showed a regional variation and gender differences. In female rat, transport rate in the jejunum was about 1.3 higher than ileum. Both ERY and CSA significant increases transport of NMD. Contrast to female, NMD transport in jejunum was lower that that in ileum. Bothe ERY and CSA had little effect on NMD transport in intestine. These results indicated that there existed gender difference in oral absorption of NMD and effect of ERY on oral absorption kinetics of NMD in female rats was different from that in male rat.

Animals↗

PubMedDate not supplied

In vitro evaluation of anticryptosporidial agents using MDCK cell culture and chemiluminescence immunoassay.

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Animals↗

PubMedDate not supplied

Muscular asthenopia and eccentric ablation after photorefractive keratectomy.

PURPOSE: To investigate the relationship between muscular asthenopia and eccentric ablation after photorefractive keratectomy (PRK). METHODS: Sixteen eyes of eight myopic patients whose muscular asthenopia was corrected by subjectively accepted spectacle prism after PRK, with visual acuity better than 0.8, were followed for 6 to 14 months. On the basis of preoperative and post-operative data and corneal topography, we calculated the total corrected corneal power using the Holladay formula and then measured the ablation eccentricity (h, millimeters) and its direction. According to the formula delta approximately equals Dh, the prism effective value (delta) caused by the eccentric ablation was computed and compared with the objectively accepted spectacle prism. RESULTS: The subjectively accepted spectacle prisms were similar to calculated values from the formula. Mean difference was 0.10 +/- 0.25delta. The direction of the subjectively accepted prism was in the direction of the ablation deviation. CONCLUSIONS: Eccentric ablation is an important cause of muscular visual asthenopia after PRK. The asthenopia may be corrected by spectacle prism. The spectacle prism value may be estimated by the formula delta approximately equals Dh.

Adult↗

PubMedDate not supplied

The impending Canadian prostate cancer epidemic.

PURPOSE: To model and forecast prostate cancer incidence and mortality in Canada to the year 2016. METHODS: Bivariate multiplicative models of prostate cancer incidence and mortality for Canadian men aged 45 years or older, linear in time and Weibull in age, were fitted using weighted non-linear regression. RESULTS: The number of incident cases of prostate cancer is forecast to increase from 11,355, observed in 1990, to 26,900 by the year 2010 and to 35,200 by the year 2016. The number of deaths are estimated to climb from 3,424, observed in 1991, to an estimated 6,300 by the year 2010, and to 7,800 by the year 2016. CONCLUSIONS: The dramatic increase in prostate cancer rates with age, coupled with the expected large increase in the elderly Canadian male population and steadily increasing prostate cancer incidence rates will produce very large increases in the number of men who will have prostate cancer over the next 20 years. This has important implications for health care delivery in the future.

Age Distribution↗