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Poor Absorption (poor + absorption)
Selected AbstractsPharmacokinetic profile and behavioral effects of gabapentin in the horseJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010R. L. TERRY Terry, R. L., McDonnell, S. M., van Eps, A. W., Soma, L. R., Liu, Y., Uboh, C. E., Moate, P. J., Driessen, B. Pharmacokinetic profile and behavioral effects of gabapentin in the horse. J. vet. Pharmacol. Therap. 33, 485,494. Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0,48 h postadministration employing liquid chromatography-tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gabapentin dosage. Nineteen quantitative measures of behaviors were evaluated. After i.v. gabapentin, the decline in plasma drug concentration over time was best described by a 3-compartment mammillary model. Terminal elimination half-life (t1/2,) was 8.5 (7.1,13.3) h. After p.o. gabapentin terminal elimination half-life () was 7.7 (6.7,11.9) h. The mean oral bioavailability of gabapentin (±SD) was 16.2 ± 2.8% indicating relatively poor absorption of gabapentin following oral administration in horses. Gabapentin caused a significant increase in sedation scores for 1 h after i.v. dose only (P < 0.05). Among behaviors, drinking frequency was greater and standing rest duration was lower with i.v. gabapentin (P < 0.05). Horses tolerated both i.v. and p.o. gabapentin doses well. There were no significant differences in and . Oral administration yielded much lower plasma concentrations because of low bioavailability. [source] How common is delayed cyclosporine absorption following liver transplantation?LIVER TRANSPLANTATION, Issue 2 2005Silvina E. Yantorno The mean time to peak absorption of cyclosporine (CsA) in liver transplant patients is approximately 2 hours, but in some patients the peak occurs later. The goal of this study was, therefore, to investigate the incidence of delayed absorption in 27 de novo liver transplant recipients receiving CsA ,10 mg/kg/day (C2 monitoring) and in 15 maintenance patients. Patients were categorized as ,normal' absorbers (C2 exceeding C4 and C6) or ,delayed' absorbers (C4 or C6 exceeding C2), and as ,good' (>800 ng/mL at C0, C2, C4, or C6) or ,poor' absorbers (C0, C2, C4 and C6 <800 ng/mL) on the day of study. Among de novo patients, 15 (56%) had ,normal' CsA absorption and 12 (44%) ,delayed' absorption. Good CsA absorption occurred in 16 patients (59%) and poor absorption in 11 (41%). The proportion of poor absorbers was similar in patients with normal (6 / 15, 40%) or delayed (5 / 12, 42%) absorption. Among the 12 delayed absorbers, 11 had peak CsA concentration at C4. Mean C0 level was significantly higher in delayed absorbers (282 ± 96 ng/mL) than in normal absorbers (185 ± 88ng/mL; P = .01). Delayed absorbers reverted to normal absorption (C2 > C4) after a median of 6 days from the day of study, and no cases of delayed absorption were found among maintenance patients. In conclusion, almost 50% of the patients had delayed CsA absorption early posttransplant; around half of these exhibited normal CsA exposure. Measurement of C4 in addition to C2 differentiates effectively between delayed and poor absorbers of CsA such that over- or underimmunosuppression can be avoided. (Liver Transpl 2005;11:167,173.) [source] Antimalarial activities of gedunin and 7-methoxygedunin and synergistic activity with dillapiolANNALS OF APPLIED BIOLOGY, Issue 2 2003S OMAR Summary Gedunin from Cedrela odorata (Meliaceae), a potent in vitro antimalarial agent, was investigated for its in vivo efficacy in CD-1 mice infected with Plasmodium berghei. When orally administered at 50 mg kg-1 day-1 for 4 days, gedunin was able to suppress the parasitaemia level by 44%. However, no clear dose-response effects were observed in the 0,100 mg kg-1 day-1 dose range. Preliminary pharmacokinetics in Sprague-Dawley rats showed poor absorption. However, a binary treatment of 50 mg kg-1 day-1 gedunin with 25 mg kg-1 day-1 dillapiol, a cytochrome P450 inhibitor, increased parasitaemia clearance in mice to 75%. A clear dose-response was observed in the 0,50 mg kg-1 day-1 gedunin dose range when administration was combined with 25 mg kg-1 day-1 dillapiol. In addition, 7-methoxygedunin, a semi-synthetic derivative which is more stable to degradation than gedunin, suppressed the level in mice by 67% at 50 mg kg-1 day-1. When administered at this dose in combination with 25 mg kg-1 day-1 dillapiol, clearance increased to 80%. These results demonstrate the potentialefficacy of antimalarial drugs and phytomedicines based on gedunin and the value of the combination therapy. [source] Curcumin in Cancer Chemoprevention: Molecular Targets, Pharmacokinetics, Bioavailability, and Clinical TrialsARCHIV DER PHARMAZIE, Issue 9 2010Adeeb Shehzad Abstract Curcumin (diferuloylmethane), a derivative of turmeric is one of the most commonly used and highly researched phytochemicals. Abundant sources provide interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancer. The pleiotropic role of this dietary compound includes the inhibition of several cell signaling pathways at multiple levels, such as transcription factors (NF-,B and AP-1), enzymes (COX-2, MMPs), cell cycle arrest (cyclin D1), proliferation (EGFR and Akt), survival pathways (,-catenin and adhesion molecules), and TNF. Curcumin up-regulates caspase family proteins and down-regulates anti-apoptotic genes (Bcl-2 and Bcl-XL). In addition, cDNA microarrays analysis adds a new dimension for molecular responses of cancer cells to curcumin at the genomic level. Although, curcumin's poor absorption and low systemic bioavailability limits the access of adequate concentrations for pharmacological effects in certain tissues, active levels in the gastrointestinal tract have been found in animal and human pharmacokinetic studies. Currently, sufficient data has been shown to advocate phase II and phase III clinical trials of curcumin for a variety of cancer conditions including multiple myeloma, pancreatic, and colon cancer. [source] Quantitative LC/MS/MS method and in vivo pharmacokinetic studies of vitexin rhamnoside, a bioactive constituent on cardiovascular system from hawthornBIOMEDICAL CHROMATOGRAPHY, Issue 4 2007Mingjin Liang Abstract A simple and accurate liquid chromatography coupled with tandem mass spectrometry method was developed for determination and in vivo pharmacokinetic studies of vitexin rhamnoside in rat plasma. After protein precipitation using methanol, the analytes were separated by a Luna C18 column with an isocratic elution and analyzed by mass spectrometry in multiple reaction monitoring mode using the respective negative ion at m/z 577.2,293.0 for vitexin rhamnoside and m/z 593.2,413.0 for internal standard (IS) vitexin glucoside. The method was validated systematically within the concentration range 5,5000 µg/L (R > 0.996) and the lower limit of quantitation was 5 µg/L. Acceptable precision and accuracy were acquired for concentrations over the standard curve range. It was further applied to assess pharmacokinetics and bioavailability of vitexin rhamnoside after intravenous and oral administration to rats. The oral bioavailability of vitexin rhamnoside was only 3.57%, which indicated that vitexin rhamnoside had poor absorption or underwent extensive first-pass metabolism. Practical utility of this new LC/MS/MS method was confirmed in pilot pharmacokinetic studies in rats following both intravenous and oral administration. Copyright © 2007 John Wiley & Sons, Ltd. [source] Review of select transplant subpopulations at high risk of failure from standard immunosuppressive therapyCLINICAL TRANSPLANTATION, Issue 5 2000Mark H Deierhoi Despite improvements in short-term graft and patient survival rates for solid organ transplants, certain subgroups of transplant recipients experience poorer clinical outcome compared to the general population. Groups including pediatrics, African-Americans, diabetics, cystic fibrosis patients, and pregnant women require special considerations when designing immunosuppressive regimens that optimize transplant outcomes. Problems specific to pediatric transplant recipients include altered pharmacokinetics of immunosuppressive drugs, such as cyclosporine (CsA) and tacrolimus (poor absorption, increased metabolism, rapid clearance), the need to restore growth post-transplantation, and a high incidence of drug-related adverse effects. African-Americans have decreased drug absorption and bioavailability, high immunologic responsiveness, and a high incidence of post-transplant diabetes mellitus. Diabetics and cystic fibrosis patients exhibit poor absorption of immunosuppressive agents, which may lead to underimmunosuppression and subsequent graft rejection. Pregnant women undergo physiologic changes that can alter the pharmacokinetics of immunosuppressives, thus requiring careful clinical management to minimize the risks of either under- or overimmunosuppression to mother and child. To achieve an optimal post-transplant outcome in these high-risk patients, the problems specific to each group must be addressed, and immunosuppressive therapy individualized accordingly. Drug formulation greatly impacts upon pharmacokinetics and the resultant level of immunosuppression. Thus, a formulation with improved absorption (e.g., CsA for microemulsion), higher bioavailability, and less pharmacokinetic variability may facilitate patient management and lead to more favorable outcomes, especially in groups demonstrating low and variable bioavailability. Other strategies aimed at improving transplant outcome include the use of higher immunosuppressive doses, different combinations of immunosuppressive agents, more frequent monitoring, and management of concurrent disease states. [source] | |||||||||||||