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Oral Solution (oral + solution)
Selected AbstractsItraconazole oral solution and intravenous formulations: a review of pharmacokinetics and pharmacodynamicsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2001L. Willems Itraconazole is a triazole antifungal agent with a broad spectrum of activity. It is well tolerated and highly efficacious, particularly because its main metabolite, hydroxy-itraconazole, also has considerable antifungal activity. Two new formulations of itraconazole, an oral solution and an intravenous formulation, have recently been developed, which combine lipophilic itraconazole with cyclodextrin. These formulations have improved the solubility of itraconazole, leading to enhanced absorption and bioavailability compared with the original capsule formulation, without having an impact on the tolerability profile of itraconazole. The oral solution and intravenous formulations of itraconazole produce consistent plasma concentrations and are ideal for the treatment of systemic fungal infections in a wide range of patient populations. The additional flexibility offered by the different routes of administration means that itraconazole treatment can be specifically tailored for use in all patients, including children and those requiring intensive care. [source] Development of patch and spray formulations for enhancing topical delivery of sinomenine hydrochlorideJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2010Xinru Li Abstract The purpose of this work was to investigate feasibility of a promising topical drug delivery system (TDDS) for sinomenine hydrochloride (SMH), extracted from the Chinese medicinal plant sinomenine acutum and currently used for the treatment of rheumatoid arthritis. It was found that SMH was a weak base (pKa, 7.98,±,0.04) with pH-dependent solubility and partition coefficient. The result of in vitro permeation studies demonstrated that the permeation enhancer azone was the most effective. In contrast, spray had higher accumulative permeated amounts of SMH than patch, but permeated duration of spray was shorter than that of patch. The efficacy on Freund's complete adjuvant-induced arthritis suggested that there was near arthritis index for SMH spray with medium dose (i.e., 15,mg/rat) and oral solution at a dose of 12,mg/rat, indicating that topical SMH delivery system could achieve the similar anti-inflammatory efficacy with oral administration. Pharmacokinetic parameters including Cmax and AUC for both topical preparations were lower than those for oral preparation, which hinted that systemic side effect could be ignored. Therefore, the spray and patch were promising formulations for successful topical delivery of SMH through the skin instead of oral administration with side effects. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1790,1799, 2010 [source] The use of three different solid dispersion formulations,melt extrusion, film-coated beads, and a glass thermoplastic system,to improve the bioavailability of a novel microsomal triglyceride transfer protein inhibitorJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2004Geert Verreck Abstract A bioavailable formulation for a water-insoluble microsomal triglyceride transfer protein inhibitor, R103757, was developed using solid dispersion technology. The need for an advanced formulation was tested in the dog by assessing the oral bioavailability of three generic concepts: a tablet (crystalline drug), a capsule (film-coated beads), and an oral solution. These screening studies steered further development in the direction of a solid dispersion. Three solid dispersion platforms were assessed: melt extrusion, film-coated beads, and a glass thermoplastic system. Thermal and spectrophotometric analysis revealed that no crystalline drug was present in any of the formulations. The dissolution profiles of the three dispersion systems showed that release was improved compared with the unmanipulated drug. In addition, stability studies confirmed the physical and chemical integrity of the formulation. A human clinical trial was performed to assess the pharmacokinetics of the three amorphous dispersions. Plasma levels were obtained after single oral administration in both the fasting and fed state. The study indicated that all three approaches improved the bioavailability of R103757 with the glass thermoplastic system providing the best performance. These studies point to the potential usefulness of solid dispersion approaches and expand the possible number of ways to implement these methodologies. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1217,1228, 2004 [source] Clinical trial: the safety and short-term efficacy of recombinant cholera toxin B subunit in the treatment of active Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2010P. STÅL Aliment Pharmacol Ther,31, 387,395 Summary Background, The cholera toxin B subunit ameliorates experimentally induced colitis in mice. In humans, cholera toxin B subunit has never been tested in the treatment of Crohn's disease (CD). Aim, To evaluate the safety and efficacy of treatment with recombinant cholera toxin B subunit of patients with CD. Methods, An open-label, multicentre, nonrandomized trial including 15 patients with mild/moderate CD. Patients received an oral solution of 5 mg recombinant cholera toxin B subunit three times weekly for 2 weeks. Reduction in CD Activity Index (CDAI) with >100 between baseline and days 15, 29, 42 and 70 defined clinical response. Patients with CDAI score ,150 were defined as being in remission. Results, A significant decrease in CDAI score was observed. Response rates were 40% in the full analysis set and 42% in the per protocol analysis. Two patients receiving adjuvant treatment after day 29 were excluded, after which 40% were in remission at 4 weeks and 30% at 8 weeks post-treatment. Mild side effects (arthralgia, headache and pruritus) were seen in 33% of patients. Conclusions, Treatment with recombinant cholera toxin B subunit was safe. Approximately 40% of patients with active CD responded to treatment. Randomized studies are needed to establish the clinical efficacy of recombinant cholera toxin B subunit. [source] Comparison of Two Oral Electrolyte Solutions and Route of Administration on the Abomasal Emptying Rate of Holstein-Friesian CalvesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2006Mohammad Nouri Dehydrated calves with diarrhea are routinely given an oral electrolyte solution (OES) by suckling or esophageal intubation. An important issue related to rehydration therapy is the rate of OES delivery to the small intestine. It is widely assumed that the glucose content of the OES does not impact the speed of resuscitation and that fluid administered by esophageal intubation provides a similar resuscitative response to that obtained by suckling. The aims of this study were to compare the abomasal emptying rate in calves suckling an OES containing a high or low glucose concentration and in calves administered a high-glucose OES by suckling or esophageal intubation. Seven male Holstein-Friesian calves were given the following treatments in random order: 2 L of a commercially available high-glucose OES ([glucose] = 405 mM) by suckling or esophageal intubation or 2 L of a commercially available low-glucose OES ([glucose] = 56 mM) by suckling. Abomasal emptying rate was determined by acetaminophen absorption, ultrasonography, and glucose absorption. High-glucose OES rapidly increased plasma glucose concentration after suckling but produced a slower rate of abomasal emptying than did low-glucose OES. Esophageal intubation of high-glucose OES produced the same initial change in abomasal volume as did suckling, but delayed the rate of OES delivery to the small intestine. Our results suggest that suckling a low-glucose OES provides the fastest rate of abomasal emptying and plasma volume expansion, whereas a high-glucose OES provides the most appropriate oral solution for treating hypoglycemic calves. [source] Pharmacokinetics of total thyroxine in dogs after administration of an oral solution of levothyroxine sodiumJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2008G. LE TRAON Oral l -thyroxine (l -T4) supplementation is used to replace thyroid hormone concentrations in dogs with hypothyroidism. The pharmacokinetics of l -T4 following administration of a solution (Leventa®) was investigated in healthy dogs. l -T4 was absorbed fairly rapidly (tmax 3 h). A mean bioavailability of 22% was calculated following a single oral administration of 40 ,g l -T4/kg body weight. Repeated oral administration at the same dose for 14 consecutive days did not lead to any accumulation of T4 in serum. After intravenous administration of l -T4, a serum half-life of 11.6 h was calculated. Food intake concomitant with l -T4 oral administration delayed l -T4 absorption and decreased its rate and extent by about 45%. The relative bioavailability of l -T4 following administration of a tablet formulation was about 50% of that of the l -T4 solution. The pharmacokinetic properties of liquid l -T4 after oral administration support the use of a dose rate of 20 ,g/kg once daily, as a starting dose for replacement therapy in dogs with hypothyroidism. [source] Valganciclovir Dosing According to Body Surface Area and Renal Function in Pediatric Solid Organ Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009W. Vaudry Oral valganciclovir is effective prophylaxis for cytomegalovirus (CMV) disease in adults receiving solid organ transplantation (SOT). However, data in pediatrics are limited. This study evaluated the pharmacokinetics and safety of valganciclovir oral solution or tablets in 63 pediatric SOT recipients at risk of CMV disease, including 17 recipients ,2 years old. Patients received up to 100 days' valganciclovir prophylaxis; dosage was calculated using the algorithm: dose (mg) = 7 × body surface area × creatinine clearance (Schwartz method; CrCLS). Ganciclovir pharmacokinetics were described using a population pharmacokinetic approach. Safety endpoints were measured up to week 26. Mean estimated ganciclovir exposures showed no clear relationship to either body size or renal function, indicating that the dosing algorithm adequately accounted for both these variables. Mean ganciclovir exposures, across age groups and organ recipient groups were: kidney 51.8 ± 11.9 ,g * h/mL; liver 61.7 ± 29.5 ,g * h/mL; heart 58.0 ± 21.8 ,g * h/mL. Treatment was well tolerated, with a safety profile similar to that in adults. Seven serious treatment-related adverse events (AEs) occurred in five patients. Two patients had CMV viremia during treatment but none experienced CMV disease. In conclusion, a valganciclovir-dosing algorithm that adjusted for body surface area and renal function provides ganciclovir exposures similar to those established as safe and effective in adults [source] Pharmacokinetics and allometric scaling of levormeloxifene, a selective oestrogen receptor modulatorBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2003O. Østerberg Abstract The pharmacokinetics of a new selective oestrogen receptor modulator levormeloxifene was investigated in mice, rats, cynomolgus monkeys and humans by compartmental pharmacokinetics. Levormeloxifene was administered as an oral solution in all studies. Allometric scaling was used to predict human pharmacokinetic parameters and the performance of the approach was evaluated. Mean values of clearance confounded by F(CL/F) were 0.073, 0.29, 3.18 and 2.4 l/h in mice, rats, monkeys and humans, respectively. Values of distribution volume at steady state confounded by F(Vss/F) were 0.073 and 7.5 l in mice and rats. In monkeys, values of the central volume F(Vc/F) and volume at steady state F(Vss/F) were 28.9 and 57.9 l, respectively. In humans, values of Vc/F and Vss/F were 106 and 587 l, respectively. Predicted CL/F and Vss/F showed a linear relationship when plotted vs BW on a log,log scale; for CL/F, r was 0.95,0.98 and for Vss/F, r was 0.99. Using allometric scaling the predicted human Vss/F deviated 3-fold from the experimentally determined values. Observed values of CL/F deviated 21,25 fold from the predicted, the latter depending on the scaling method. Confidence intervals for the predicted parameters showed major lack of precision for all the allometric scaling methods. Copyright © 2003 John Wiley & Sons, Ltd. [source] Pharmacokinetics of tamoxifen after intravenous and oral dosing of tamoxifen,hydroxybutenyl-,-cyclodextrin formulationsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 3 2007Charles M. Buchanan Abstract Oral and intravenous administration of tamoxifen base and tamoxifen citrate formulated with hydroxybutenyl-,-cyclodextrin (HBenBCD) to Sprague,Dawley rats significantly increased the oral bioavailability of tamoxifen relative to that of parent drug (no HBenBCD). When formulated with HBenBCD, the form of tamoxifen (base vs. salt) made no difference in the oral bioavailability of tamoxifen. Liquid formulations (PG:PEG400:H2O) provided higher oral bioavailability than solid formulations dissolved and dosed as aqueous oral solutions. The oral bioavailability of tamoxifen was significantly influenced by both dietary status and time of dosing of the animals. Tamoxifen metabolite plasma concentrations were not affected by complexation of tamoxifen with HBenBCD. Collectively, the data indicated that dosing of fasted animals in the morning with tamoxifen:HBenBCD formulations provided a very significant increase in tamoxifen oral bioavailability (up to 10- to 14-fold). © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci [source] | ||||||||||