Pharmacokinetics analysis

Tsukamoto Y, Kato Y, Ura M, Horii I, Ishitsuka H, Kusuhara H, Sugiyama Y. A physiologically based pharmacokinetic analysis of capecitabine, a triple prodrug of 5-FU, in humans the mechanism for tumor-selective accumulation of 5-FU. Pharm Res 2001 Aug 18(8) 1190-202. 

Obtain serum drug levels for aminoglycosides and/or vancomycin and perform pharmacokinetic analysis. Adjust the dose, if needed, according to the parameters in Table 13-2. Obtain follow-up trough levels at weekly intervals or sooner if renal function is unstable. Follow serum creatinine levels if renal function is unstable. Hearing tests may be scheduled yearly or per patient preference. 

K. Murata, K. Noda, K. Kohno, M. Sam ej ima. Pharmacokinetic analysis of concentration data of drugs with irregular absorption profiles using multi-function absorption models. /. Pharm. Sci. 1987, 76, 109-113. 

If the unbound drug concentrations in plasma are higher than their K values on the transporters, then transporter function may be significantly affected [106], Following a pharmacokinetic analysis of the effect of probenecid on the hepatobiliary excretion of methotrexate, it has been shown the extent of an in vivo drug-drug interaction can be quantitatively predicted from the kinetic parameters for transport across the sinusoidal and bile canalicular membranes determined in vitro [107]. 

Parkhurst et al. [79] described a high performance liquid chromatographic method for the simultaneous determination of primaquine and its metabolites from plasma and urine samples, utilizing acetonitrile deproteinization, and direct injection onto a cyano column. Levels of 100 ng/mL per 20 pL injection could be quantitated. Preliminary pharmacokinetic analysis is reported for two human subjects after oral doses of 60 90 mg primaquine diphosphate. Two apparent plasma metabolites and two possible urinary metabolites are also reported. 

Karara, A.H. and V.A. McFarland. 1992. A pharmacokinetic analysis of the uptake of polychlorinated biphenyls (PCBs) by golden shiners. Environ. Toxicol. Chem. 11 315-320. 

Jen, J.F. et al., Population pharmacokinetic analysis of pegylated interferon alfa-2b and interferon alfa-2b in patients with chronic hepatitis C, Clin. Pharmacol. Then, 69, 407, 2001. 

For plasma and blood experiments, LC effluent was directed to waste for the first 1 min. Conventional blood analysis by drawing 1 mL samples from the saphenous catheter was used to validate SPME results. These samples were subjected to PPT with acetonitrile and the supernatant from centrifugation was analyzed. The SPME probes were also evaluated for pharmacokinetic analysis of diazepam and its metabolites, oxazepam and nordiazepam. Good correlation was obtained for conventional blood drawn from saphenous and cephalic sites of the animals, as shown in Figure 1.48. Although the analytical parameters for the automated study need improvement, the authors cite the study as a first demonstration of SPME technology for in vivo analysis. 

No modern studies of the human pharmacokinetics of LSD have been done, largely because human experimentation has virtually stopped. An older study that used a spectrofluorometric technique for measuring plasma concentrations of LSD was done in humans given doses of 2 Mg/kg i.v. After equilibration had occurred in about 30 min, the plasma level was between 6 and 7 ng/ml. Subsequently, plasma levels gradually fell until only a small amount of LSD was present after 8 hr. The half-life of the drug in humans was calculated to be 175 min (2). Subsequent pharmacokinetic analysis of these data indicated that plasma concentrations of LSD were explained by a two-compartment open model. Performance scores were highly correlated with concentration in the tissue (outer) compartment, which was calculated at 11.5% of body weight. The new estimation of half-life for loss of LSD from plasma, based on this model, was 103 min (47). 

Drug Levels in Plasma. Drug levels may also be measured in a clinical trial. Such levels are usually part of a pharmacokinetic analysis but also provide important safety data. This information would be particularly relevant in cases of suspected or actual drug overdosage, drug interactions, to correlate medicine levels with toxic events, or in other situations. It must be clarified whether free levels of the drug and/or the protein bound will be measured by the laboratory. 

Ajayakumar P.V. Chanda D. Pal A. Singh M.P. Samad A. FT-NIR spectroscopy for rapid and simple determination of nimesulide in rabbit plasma for pharmacokinetic analysis. Journal of Pharmaceutical and Biomedical Analysis, 2012, 58 (1), 157-162. 

H. Salim, K. Badir, A. Haj Yeshia, M. Bialer, Pharmacokinetic Analysis of Ester Prodrugs of Valproic Acid , Pharm. Res. 1990, 7, S222. 

E. Samara, D. Avnir, D. Ladkani, M. Bialer, Pharmacokinetic Analysis of Diethyl-carbonate Prodrugs of Ibuprofen and Naproxen , Biopharm. Drug Dispos. 1995, 16, 201-210. 

Y. Tsukamoto, Y. Kato, M. Ura, I. Horii, H. Ishitsuka, H. Kusuhara, Y. Sugiyama, A physiologically Based Pharmacokinetic Analysis of Capecitabine, a Triple Prodrug of 5-FU, in Humans The Mechanism for Tumor-Selective Accumulation of 5-FU , Pharm. Res. 2001, 18, 1190-1202. 

It may be concluded that, so far, a pharmacokinetic analysis of antidepressants is of limited clinical value because of ... 

Fig. 2.2 I nter-relationship between various terms of drug clearance used within pharmacokinetic analysis. 

Although, like statistics, the details of pharmacokinetic analysis are best left to the experts, a pharmaceutical physician who is familiar with the basic concepts of how pharmacokinetic information contributes to a dossier will be able to interact more effectively with company colleagues and regulatory authority staff, it is the aim of this chapter to provide such a preliminary grounding. 

In order to appreciate the difference in approach, it is necessary to describe how pharmacokinetic analysis is traditionally performed. In a typical conventional pharmacokinetic study, a large number of samples is taken from a limited... 

Pharmacokinetics Population pharmacokinetic analysis gave the following values for a reference patient (white male, 45 years of age, with a body weight of 80 kg and no proteinuria) Systemic clearance is 15 mL/h, volume of central compartment is P.1160... 

Takanaga H, Ohnishi A, Matsuo H, et al. Pharmacokinetic analysis of felodi-pine-grapefruit juice interaction based on an irreversible enzyme inhibition model. Br J Clin Pharmacol 2000 49 49-58. 

Addiiloni) populaliun pharmacokinetic analysis may assist the overall evaluation... 

Fruit juices such as grapefruit, orange, and apple may reduce the bioavailability and exposure of fexofenadine. This is based on the results from three clinical studies using histamine-induced skin wheals and flares coupled with population pharmacokinetic analysis. Therefore, to maximize the effects of fexofenadine, it is recommended that ALLEGRA-D 24 HOUR should be taken with water... 

Rohatagi S, Krishnaswami S, Pfister M, Sahasranaman S. Model-based covariate pharmacokinetic analysis and lack of cortisol suppression by the new inhaled corticosteroid ciclesonide using a novel cortisol release model. Am J Ther... 

The evaluation of pharmacokinetic analysis of resveratrol was carried out in different animal models such as rats, mice, and rabbits [Asensi et al., 2002 Chen et al., 2007 Juan et al., 2002 Marier et al., 2002 Sale et al., 2004] furthermore, pharmacokinetic analysis was also evaluated with other resveratrol derivatives such as piceid [Lv et al., 2006 Zhou et al., 2007], a Smilax china root extract [Huang et al., 2008], 3,4,5,4 -tetramethoxystilbene [Sale et al., 2004], piceatan-nol, pinosylvin, and rhapontigenin [Roupe et al., 2006] (Table 13.4). 

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