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Yuji Kumagai - One of the best experts on this subject based on the ideXlab platform.
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A drug–drug interaction study of a novel, selective urate reabsorption inhibitor dotinurad and the non-steroidal anti-inflammatory drug Oxaprozin in healthy adult males
Clinical and Experimental Nephrology, 2020Co-Authors: Kenichi Furihata, Katsuaki Nagasawa, Atsushi Hagino, Yuji KumagaiAbstract:Background Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug Oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug–drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with Oxaprozin. Methods This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without Oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. Results This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with Oxaprozin compared to administration of dotinurad alone was 0.657 (0.624–0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity (AUC_0–inf) were 0.982 (0.945–1.021) and 1.165 (1.114–1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of Oxaprozin alone. Conclusions In comparison with administration of dotinurad alone, co-administration with Oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC_0–inf of dotinurad. However, no clinically meaningful drug–drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with Oxaprozin. Clinical trial registration ClinicalTrials.gov Identifier: NCT03350386.
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a drug drug interaction study of a novel selective urate reabsorption inhibitor dotinurad and the non steroidal anti inflammatory drug Oxaprozin in healthy adult males
Clinical and Experimental Nephrology, 2020Co-Authors: Kenichi Furihata, Katsuaki Nagasawa, Atsushi Hagino, Yuji KumagaiAbstract:Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug Oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug–drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with Oxaprozin. This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without Oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with Oxaprozin compared to administration of dotinurad alone was 0.657 (0.624–0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity (AUC0–inf) were 0.982 (0.945–1.021) and 1.165 (1.114–1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of Oxaprozin alone. In comparison with administration of dotinurad alone, co-administration with Oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC0–inf of dotinurad. However, no clinically meaningful drug–drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with Oxaprozin. ClinicalTrials.gov Identifier: NCT03350386.
Kenichi Furihata - One of the best experts on this subject based on the ideXlab platform.
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A drug–drug interaction study of a novel, selective urate reabsorption inhibitor dotinurad and the non-steroidal anti-inflammatory drug Oxaprozin in healthy adult males
Clinical and Experimental Nephrology, 2020Co-Authors: Kenichi Furihata, Katsuaki Nagasawa, Atsushi Hagino, Yuji KumagaiAbstract:Background Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug Oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug–drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with Oxaprozin. Methods This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without Oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. Results This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with Oxaprozin compared to administration of dotinurad alone was 0.657 (0.624–0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity (AUC_0–inf) were 0.982 (0.945–1.021) and 1.165 (1.114–1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of Oxaprozin alone. Conclusions In comparison with administration of dotinurad alone, co-administration with Oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC_0–inf of dotinurad. However, no clinically meaningful drug–drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with Oxaprozin. Clinical trial registration ClinicalTrials.gov Identifier: NCT03350386.
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a drug drug interaction study of a novel selective urate reabsorption inhibitor dotinurad and the non steroidal anti inflammatory drug Oxaprozin in healthy adult males
Clinical and Experimental Nephrology, 2020Co-Authors: Kenichi Furihata, Katsuaki Nagasawa, Atsushi Hagino, Yuji KumagaiAbstract:Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug Oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug–drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with Oxaprozin. This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without Oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with Oxaprozin compared to administration of dotinurad alone was 0.657 (0.624–0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity (AUC0–inf) were 0.982 (0.945–1.021) and 1.165 (1.114–1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of Oxaprozin alone. In comparison with administration of dotinurad alone, co-administration with Oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC0–inf of dotinurad. However, no clinically meaningful drug–drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with Oxaprozin. ClinicalTrials.gov Identifier: NCT03350386.
Katsuaki Nagasawa - One of the best experts on this subject based on the ideXlab platform.
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A drug–drug interaction study of a novel, selective urate reabsorption inhibitor dotinurad and the non-steroidal anti-inflammatory drug Oxaprozin in healthy adult males
Clinical and Experimental Nephrology, 2020Co-Authors: Kenichi Furihata, Katsuaki Nagasawa, Atsushi Hagino, Yuji KumagaiAbstract:Background Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug Oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug–drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with Oxaprozin. Methods This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without Oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. Results This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with Oxaprozin compared to administration of dotinurad alone was 0.657 (0.624–0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity (AUC_0–inf) were 0.982 (0.945–1.021) and 1.165 (1.114–1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of Oxaprozin alone. Conclusions In comparison with administration of dotinurad alone, co-administration with Oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC_0–inf of dotinurad. However, no clinically meaningful drug–drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with Oxaprozin. Clinical trial registration ClinicalTrials.gov Identifier: NCT03350386.
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a drug drug interaction study of a novel selective urate reabsorption inhibitor dotinurad and the non steroidal anti inflammatory drug Oxaprozin in healthy adult males
Clinical and Experimental Nephrology, 2020Co-Authors: Kenichi Furihata, Katsuaki Nagasawa, Atsushi Hagino, Yuji KumagaiAbstract:Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug Oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug–drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with Oxaprozin. This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without Oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with Oxaprozin compared to administration of dotinurad alone was 0.657 (0.624–0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity (AUC0–inf) were 0.982 (0.945–1.021) and 1.165 (1.114–1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of Oxaprozin alone. In comparison with administration of dotinurad alone, co-administration with Oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC0–inf of dotinurad. However, no clinically meaningful drug–drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with Oxaprozin. ClinicalTrials.gov Identifier: NCT03350386.
Atsushi Hagino - One of the best experts on this subject based on the ideXlab platform.
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A drug–drug interaction study of a novel, selective urate reabsorption inhibitor dotinurad and the non-steroidal anti-inflammatory drug Oxaprozin in healthy adult males
Clinical and Experimental Nephrology, 2020Co-Authors: Kenichi Furihata, Katsuaki Nagasawa, Atsushi Hagino, Yuji KumagaiAbstract:Background Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug Oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug–drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with Oxaprozin. Methods This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without Oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. Results This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with Oxaprozin compared to administration of dotinurad alone was 0.657 (0.624–0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity (AUC_0–inf) were 0.982 (0.945–1.021) and 1.165 (1.114–1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of Oxaprozin alone. Conclusions In comparison with administration of dotinurad alone, co-administration with Oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC_0–inf of dotinurad. However, no clinically meaningful drug–drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with Oxaprozin. Clinical trial registration ClinicalTrials.gov Identifier: NCT03350386.
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a drug drug interaction study of a novel selective urate reabsorption inhibitor dotinurad and the non steroidal anti inflammatory drug Oxaprozin in healthy adult males
Clinical and Experimental Nephrology, 2020Co-Authors: Kenichi Furihata, Katsuaki Nagasawa, Atsushi Hagino, Yuji KumagaiAbstract:Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug Oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug–drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with Oxaprozin. This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without Oxaprozin, we compared its pharmacokinetic parameters and evaluated safety. This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with Oxaprozin compared to administration of dotinurad alone was 0.657 (0.624–0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration–time curve from time zero to infinity (AUC0–inf) were 0.982 (0.945–1.021) and 1.165 (1.114–1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of Oxaprozin alone. In comparison with administration of dotinurad alone, co-administration with Oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC0–inf of dotinurad. However, no clinically meaningful drug–drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with Oxaprozin. ClinicalTrials.gov Identifier: NCT03350386.
Marijke H Adams - One of the best experts on this subject based on the ideXlab platform.
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Oxaprozin and piroxicam nonsteroidal antiinflammatory drugs with long half lives effect of protein binding differences on steady state pharmacokinetics
The Journal of Clinical Pharmacology, 1997Co-Authors: Aziz Karim, Gilbert F Mcmahon, Robert J Noveck, Margo Smith, Sharon Crosby, Marijke H Adams, John H WiltonAbstract:The nonsteroidal antiinflammatory drugs (NSAIDs) Oxaprozin and piroxicam have long elimination half-lives (t 1/2 approximately 55 hours), permitting once-daily dose regimens. The protein-binding characteristics of these drugs, however, vary widely. This study examines the effect of these binding differences on the drugs' disposition kinetics at steady state. A total of 52 participants (26 young healthy volunteers, and 26 elderly osteoarthritic patients, 15 men and 37 women (2 of them poor metabolizers of debrisoquine [CYP2D6]) completed the two-period, two-treatment, randomized, single-dose and 21-day, once-daily multiple-dose, cross-over study. Doses of Oxaprozin and piroxicam were 1,200 mg once daily and 20 mg once daily, respectively. Mean single-dose kinetic parameters of Oxaprozin versus piroxicam did not differ more than +/-14% (t1/2, 53.0 versus 57.4 hours; apparent oral clearance adjusted for 70-kg body weight [Clpo], 0.139 versus 0.121 L/hr; apparent volume of distribution adjusted for 70-kg body weight [Vd/F]; 10.2 L versus 9.13 L). Protein binding was plasma-concentration dependent with Oxaprozin (range, 10-400 mg/L) but not with piroxicam (range, 1-30 mg/ L). Steady-state conditions were established within 3 days with Oxaprozin but took almost 12 days with piroxicam. Compared with the single-dose values, steady-state Clpo (Clpo,ss) and Vd/F of total drug increased with Oxaprozin by almost 127% but remained within +/-10% with piroxicam. Post-steady-state apparent t 1/2 of the total and unbound drugs of approximately 62 hours were similarly prolonged with piroxicam but differed substantially with Oxaprozin (50.6 hours [total drug] versus 23.8 hours [unbound drug]). Single dose Clpo (Clpo,sd) values of both NSAIDs were significantly correlated in the study populations. With both NSAIDs, Clpo in the two poor metabolizers of debrisoquine was within +/-20% of mean values for the population. Clinically important age- and gender-dependent decreases were not observed in the weight-adjusted, Clpo,sd or Vd/F values of the total drug for either NSAID. Clearances of the two NSAIDs were significantly correlated, suggesting that a common P450 isozyme (most likely CYP2C9, in that piroxicam is a known substrate of this isozyme) may be at least partly involved in the oxidative metabolism of these NSAIDs.
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False-positive Benzodiazepine Urine Test Due to Oxaprozin-Reply
JAMA: The Journal of the American Medical Association, 1995Co-Authors: Harvey Raphan, Marijke H AdamsAbstract:In Reply. —We thank Dr Pulini for her interest in this issue. Laboratory test interferences have been reported by Jelic-Ivanovic et al 1 and in the complete prescribing information for several NSAIDs, including etodolac (Lodine, Wyeth-Ayerst Laboratories, Philadelphia, Pa), naproxen sodium (Anaprox, Naprosyn; Syntex Puerto Rico Inc), fenoprofen calcium (Nalfon, Eli Lilly and Co, Indianapolis, Ind), and tolmetin sodium (Tolectin, McNeil Pharmaceuticals, Raritan, NJ), and GD Searle & Co has received reports of alleged false-positive benzodiazepine test results from standard urine toxicology screens for drugs of abuse in patients taking Oxaprozin. Based on our investigation into this matter, the prescribing information for Oxaprozin was updated in November 1993 to reflect the new information. The 1994 Physicians' Desk Reference (PDR) had already gone to press at that time; current information appears in the 1995 PDR and in the PDR on CD-ROM. 2 Although Oxaprozin is not chemically related to the benzodiazepines,
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The effect of co-administered drugs on Oxaprozin binding to human serum albumin.
The Journal of pharmacy and pharmacology, 1995Co-Authors: Anne-françoise Aubry, Marijke H Adams, Nektaria Markoglou, James Longstreth, Irving W. WainerAbstract:The binding of the non-steroidal anti-inflammatory drug Oxaprozin to human serum albumin was studied by bioaffinity high-performance liquid chromatography using a column based on immobilized human serum albumin. Displacement studies using marker compounds for the major drug binding sites showed that Oxaprozin has a high affinity for the benzodiazepine/indole site and binds to the warfarin site but with a significantly lower affinity. Biochromatography and ultrafiltration techniques were used to screen for possible competition and allosteric interactions between Oxaprozin and potential co-administered drugs including non-steroidal anti-inflammatory drugs, antipyretics, hypoglycaemics, inhibitors of angiotensin-converting enzyme, anaesthetics, metal ions and anticancer agents. Competition occurred mainly with drugs bound at the benzodiazepine site (benzodiazepines, various non-steroidal anti-inflammatories).
