Pharmacokinetics maximum plasma concentration

Pharmacokinetics Disulfiram is slowly absorbed from the Gl tract and eliminated slowly from the body. The average time to reach maximum plasma concentrations... 

Pharmacokinetics The absolute bioavailability after a 70 mg subcutaneous bolus injection in healthy subjects (n = 11) is 95%. In subjects with RA, maximum plasma concentrations occurred 3 to 7 hours after subcutaneous administration of anakinra at clinically relevant doses (1 to 2 mg/kg n = 18) the terminal half-life ranged from 4 to 6 hours. In RA patients, no unexpected accumulation was observed after daily subcutaneous doses for up to 24 weeks. The estimated clearance increased with increasing Ccr and body weight. 

In terms of pharmacokinetics, letrozole is well absorbed following 2.5-mg oral administration in healthy postmenopausal women. The maximum plasma concentration of... 

Pharmacokinetics Lepirudin is eliminated primarily by renal excretion (renal clearance 65 to 115ml/min). Dose adjustment based on creatinine clearance is recommended. The total clearance of lepirudin is 195ml/min, its elimination half-life is 1.3 hours, and its volume of distribution is 12.2 to 18.0 hters.The systemic clearance of lepirudin in women is about 25% lower than in men. In elderly patients the systemic clearance of lepirudin is 20% lower than in younger patients. Distribution is limited to extracellular space. As the intravenous dose is increased over the range of 0.1 to 0.4mg/kg, the maximum plasma concentration and the area-under-the-curve increase proportionally. 

Animal studies Early pharmacokinetic studies in mice report that maximum plasma concentrations of hypericin and pseudohypericin were reached at six hours and were maintained for at least eight hours. The aqueous-ethanolic SJW extract used in this study contained 1.0 mg of hypericin (77). 

Pharmacokinetic studies in pigs following a single oral administration of 20 mg kitasamycin/kg bw showed that the drug was rapidly absorbed and distributed in the body. A maximum plasma concentration of 4.5 ppm was attained within 0.5 h, the half-life in plasma being 0.7 h. Highest tissue residue concentrations (21 ppm) were detected in kidney within 1-2 h. The ratio of the maximum concentrations determined in kidney to that in liver was around 3 2. 

Pharmacokinetic studies showed that 30 min after oral administration of 20 mg furosemide/kg bw in dogs, 22.73 ppb was the maximum plasma concentration attained. The oral bioavailability of the compound was estimated at approximately 77%. Furosemide is extensively bound to plasma proteins (91%). In dogs, the elimination half-life of furosemide was found to be 1.42 h after oral dosing, and... 

A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed [33] and validated for the determination of donepezil in human plasma samples. Diphenhydramine was used as the IS. The collision-induced transition m/z 380 > 91 was used to analyze donepezil in selected reaction monitoring mode. The signal intensity of the m/z 380 —> 91 transition was found to relate linearly with donepezil concentrations in plasma from 0.1 to 20.0 ng/ml. The lower limit of quantification of the LC/MS/MS method was 0.1 ng/ml. The intra- and inter-day precisions were below 10.2% and the accuracy was between 2.3% and +2.8%. The validated LC/MS/MS method was applied to a pharmacokinetic study in which healthy Chinese volunteers each received a single oral dose of 5 mg donepezil hydrochloride. The non-compartmental pharmacokinetic model was used to fit the donepezil plasma concentration-time curve. Maximum plasma concentration was... 

In the elderly there is a consistent increase in the maximum plasma concentration and the ti/2 of zolpidem. This is related to a reduced volume of distribution associated with a decrease in clearance [36], As with other hypnotics that are extensively degraded in the liver and show high protein binding, the pharmacokinetics of zolpidem is altered in patients with liver disease. Accordingly, in patients with hepatic insufficiency receiving zolpidem, the Cmax and the ti/2 are consistently increased [36, 37], In patients with renal insufficiency the disposition rate of zolpidem is decreased compared with that of age-matched healthy adults (Tab. 3). 

As noted in 320.24, several in vivo and in vitro methods can be used to measure product quality BA and establish BE. In descending order of preference, these include pharmacokinetic, pharmacodynamic, clinical, and in vitro studies. These general approaches are discussed in the following sections of this guidance. Product qualities BA and BE frequently rely on pharmacokinetic measures such as area under the curve (AUC) and maximum plasma concentration (Cmax) that are reflective of systemic exposure. 

Figure 16 Changes to pharmacokinetic parameters over 13-week dosing regimen. (A) Maximum plasma concentration (Cmax) of DFP determined after single doses of 10, 30, or 100 mg/kg of DFP compared to the Cmax after 13 weeks of dosing. (B) AUC after a single dose of 10, 30, or 100 mg/kg of DFP compared with the Cmax after 13 weeks of dosing. Abbreviations DFP, [(5,5-dimethyl-3-(2-propoxy)-4-(4-methanesulfonylphenyl)-2(5//)-furanone)J AUC, area under the plasma concentrationtime curve. Source From Ref. 64.

The choice of the concentration of the drug to be tested should consider therapeutic levels that could be attained with clinically employed doses. In the case of a compound under pre-clinical evaluation for a potential antitumor activity, a concentration limit of 100 pg/ml is recommended. Pharmacokinetic data are available for various anti-neoplastic clinically used drugs, with information about their maximum plasma concentration, concentration versus time, and pharmaceutical half-life in plasma. When these data are not available, an approximation of plasma levels could be obtained by calculating the theoretical concentration obtained when the administered dose is uniformly distributed throughout the body fluid. 

The pharmacokinetics of modafinil are not affected, to a clinically significant extent, by volunteer age or food intake, but both the maximum plasma concentration and the elimination half-life of the drug are increased in patients with hepatic or renal impairment. It was found that peak plasma concentrations of modafinil were reached 2.3 h after a single 200 mg oral dose in healthy volunteers. Over the dose range 200 to 600 mg, the pharmacokinetics of modafinil were linear and dose dependent. Orally administered modafinil is extensively biotransformed in the liver to the inactive metabolites modafinil acid 6 (major metabolite) and modafinil sulphone 7 (minor metabolite), before being eliminated primarily in the... 

The pharmacokinetic properties of fluoroquinolone antibacterial agents have been well described [23]. Gemifloxacin is rapidly absorbed with a time to maximum plasma concentration (T ax) of 0.5-2 h in healthy subjects and displays linear pharmacokinetics over the dose range studied (20-800 mg), with an apparent plasma terminal half-life (fi/2) after single or repeated administration of about 8 h. A minimum of 20-30% of the oral dose is excreted imchanged in the urine. Following repeat oral... 

The average drug input fluxes during the 20 min dosing periods between hours 24 and 25 were calculated to be 81, 108, and 138pg/h/cm for currents of 150, 200, and 250 pA, respectively. These values, the mean maximum plasma concentration values, and the total AUC values (over the same time period) for the three IDDS treatments all increased proportionally with current. These results agree with theoretical expectations expressed by [Eq. (1)]. In addition, the variabilities in the fentanyl pharmacokinetic parameters were similar for the IDDS and IV treatments, indicating that the IDDS doses were delivered with an accuracy similar to the IV infusions. 

Qarithromycin (500 mg bd for 10 days) significantly increased the steady-state maximum plasma concentration and the steady-state AUC of loratadine (10 mg/day for 10 days) (92). In contrast, the addition of loratadine did not affect the steady-state pharmacokinetics of clarithromycin or its active metabolite, 14(R)-hydroxyclarithromycin. No QTc interval exceeded 439 ms in any subject. 

Pharmacokinetic Tools to Characterize Absorption Kinetics. The sustained character of lung absorption is important for the degree of pulmonary selectivity. It is therefore important to evaluate lung absorption with pharmacokinetic tools. Several tools have been used to provide this information, including the time to reach the maximum plasma concentration (tmax), the mean absorption time (MAT), flip-flop, and deconvolution. These approaches are described next. 

Clomipramine is rapidly absorbed following oral administration. Maximum plasma concentrations occur within 2 hours. It is highly protein-bound (>90%) in the blood and has a half-life of 19 to 37 hours.The drug is metabolized to desmethylclomipramine, which is pharmacologically active. The pharmacokinetics of the SSRIs are discussed in Chapter 67. 

Pharmacokinetic experiments conducted in rats and man demonstrate that hyperforin 10 is absorbed after oral application [225]. After administration of 300 mg/kg of an ethanolic Hypericum extract containing 4.93% hyperforin 10 to rats, maximum plasma concentration was found to be 370 ng/ml reached after 3 h. Elimination half-life was 3 h, clearance (Cl) 70 ml/min/kg. 

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