Pharmacokinetic profile maximum plasma concentration

Ohzawa et al [112] studied the absorption, distribution, and excretion of 14C miconazole in rats after a single administration. After the intravenous administration of 14C miconazole at a dose of 10 mg/kg to the male rats, the plasma concentration of radioactivity declined biophysically with half-lives of 0.76 h (a phase) and 10.32 h (/ phase). After oral administration of 14C miconazole at a dose of 1, 3, or 10 mg/kg to male rats, the plasma concentration of radioactivity reached the maximum level within 1.25 h, after dosing and the decline of radioactivity after the maximum level was similar to that after intravenous administration. At a dose of 30 mg/kg, the pharmacokinetic profile of radioactivity in the plasma was different from that at the lower doses. In the female rats, the plasma concentration of radioactivity declined more slowly than that in male rats. The tests were conducted on pregnant rats, lactating rats, bile-duct cumulated male rats. Enterohepatic circulation was observed. In the in situ experiment, 14C miconazole injected was observed from the duodenum, jejunum, and/or ileum, but not from the stomach. 

Phase I clinical evaluation of BMS 599626 is ongoing [79,80] however, no efficacy data have been reported to date. Dose escalation has proceeded to 660 mg/day and is ongoing since a MTD has not been reached. The pharmacokinetic profile in both healthy volunteers and cancer patients supports once-daily dosing with a half-life of ca. 20 h. An area under the curve of ca. 2.4 xgh/ml with a maximum concentration of ca. 0.18 xg/ml was achieved at steady state after 100-mg dosing in patients. In mice at a dose that resulted in modest antitumor activity (ca. 50% TGI), significantly higher plasma levels were achieved (AUC ca. 14.5 xgh/ml and Cmax ca. 5.0 xg/ml) [76]. 

Renal function impairment The pharmacokinetics of diltiazem and verapamil in patients with impaired renal function are similar to the pharmacokinetic profile of patients with normal renal function. However, caution is still advised. Nifedipine s plasma concentration is slightly increased in patients with renal impairment. Nicardipine s mean plasma concentrations, AUC and maximum concentration were about 2-fold higher in patients with mild renal impairment. 

Rectal bioavailability and pharmacokinetics. Serenoa repens extract, administered rectally to 12 healthy male volunteers at a dose of 640 mg/person, produced the mean maximum concentration in plasma of nearly 2.60 (Xg/mL approx 3 hours after administration, with mean value for the area under the curve AUC 10 (Xg/hour/mL. The bioavailability and pharmacokinetic profile were similar to those observed after oral administration. T j occurred approx 1 hour later, and plasma concentration 8 hours after drug administration was still quantified. The drug tolerability was good, and no adverse effect was observed ". Serenoa repens capsules, administered orally at a dose of 160 mg four times daily or rectally 640 mg daily for 30 days to 60 patients with BPH, produced no significant differences in diminu-... 

Following a single intramuscular injection of oxytetracycline to European eels at a dosage of 60 mg/kg bw, maximum plasma oxytetracycline concentration (113 ppm) were achieved between 8 and 16 h after administration (240). At 3 weeks after drug administration, highest residue concentrations were in liver (21.7 ppb) and bones (30.2 ppb), whereas kidney, spleen, and muscle contained 6.0, 5.5, and 3.6 ppb. This experiment demonstrated that the pharmacokinetic profile of intramuscularly injected oxytetracycline to eel differed largely from those in rainbow trout, carp, and catfish (241). 

Kita et al. [154] have undertaken a study to help predict the optimal dosage of omeprazole for extensive metabolizers in the anti-H. pylori therapy. Seven healthy Japanese subjects, classified based on the CYP2C19 genotype into extensive metabolizers (n = 4) and poor metabolizers (ft = 3), participated in this study. Each subject received a single oral dose of omeprazole 20, 40, and 80 mg, with at least a 1-week washout period between each dose. Plasma concentrations of omeprazole and its two metabolites were monitored for 12 h after each dose of medication. After each dose was administered, the pharmacokinetic profiles of omeprazole and its two metabolites were significantly different between extensive metabolizers and poor metabolizers. The area under the plasma concentration-time curve of omeprazole in extensive metabolziers was disproportionally increased 3.2- or 19.2-fold with dose escalation from 20 to 40 to 80 mg omeprazole, respectively. In contrast, the area under the plasma concentration-time curve of omeprazole was proportionally increased with the higher dose in poor metabolizers. The area under the plasma concentration-time curve of omeprazole after 20 mg administration to poor metabolizers was almost equal to the area under the plasma concentration-time curve in extensive metabolizers after 80 mg administration. The recommended dose of omeprazole for extensive metabolizers is a maximum of 80 mg x 2/day based on pharmacokinetic considerations. 

The clinical development stage comprises three distinct components or phases (I, II, and III), and culminates in the filing of the NDA/MAA. Each phase involves process scale-up, pharmacokinetics, drug delivery, and drug safety activities. During phase I clinical development, the compound s safety and pharmacokinetic profile is defined. The determination of maximum concentration at steady state (Cmax), area under the plasma concentration time curve (AUC), elimination half-life, volume of distribution, clearance and excretion, and potential for drug accumulation is made in addition to studies that provide estimates of efficacious doses. Dose levels typically... 

The pharmacokinetic profile of HL6-7 was similar to that of HI-6. The mean absorption half-time of HL6-7 was about 14 min after intramuscular administration. Maximum HL6-7 concentration in plasma was reached after 30 min and the half-time of elimination was about 45 min (Eyer et al, 1992). 

The muraglitazar pharmacokinetic parameters for the unchanged drug and radioactivity are presented in Table 18.5. The animal and human plasma concentration time profiles for radioactivity and muraglitazar are presented in Fig. 18.1. Following oral administration, the radioactivity and muraglitazar concentrations reached a maximum at 0.5-1 h in rats, dogs, monkeys, and humans. 

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