scholarly journals Comparative Effects of Metamizole (Dipyrone) and Naproxen on Renal Function and Prostacyclin Synthesis in Salt-Depleted Healthy Subjects - A Randomized Controlled Parallel Group Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Lea S Blaser ◽  
Urs Duthaler ◽  
Jamal Bouitbir ◽  
Anne B Leuppi-Taegtmeyer ◽  
Evangelia Liakoni ◽  
...  
Keyword(s):  
Renal Function ◽  
Urinary Excretion ◽  
Healthy Subjects ◽  
Pharmacokinetic Parameters ◽  
Short Term Treatment ◽  
Randomized Controlled ◽  
Parallel Group Study ◽  
Parallel Group ◽  
Repeated Dosing ◽  
Prostacyclin Synthesis

Aim: The objective was to investigate the effect of metamizole on renal function in healthy, salt-depleted volunteers. In addition, the pharmacokinetics of the four major metamizole metabolites were assessed and correlated with the pharmacodynamic effect using urinary excretion of the prostacyclin metabolite 6-keto-prostaglandin F1α.Methods: Fifteen healthy male volunteers were studied in an open-label randomized controlled parallel group study. Eight subjects received oral metamizole 1,000 mg three times daily and seven subjects naproxen 500 mg twice daily for 7 days. All subjects were on a low sodium diet (50 mmol sodium/day) starting 1 week prior to dosing until the end of the study. Glomerular filtration rate was measured using inulin clearance. Urinary excretion of sodium, potassium, creatinine, 6-keto-prostaglandin F1α, and pharmacokinetic parameters of naproxen and metamizole metabolites were assessed after the first and after repeated dosing.Results: In moderately sodium-depleted healthy subjects, single or multiple dose metamizole or naproxen did not significantly affect inulin and creatinine clearance or sodium excretion. Both drugs reduced renal 6-keto-prostaglandin F1α excretion after single and repeated dosing. The effect started 2 h after intake, persisted for the entire dosing period and correlated with the concentration-profile of naproxen and the active metamizole metabolite 4-methylaminoantipyrine (4-MAA). PKPD modelling indicated less potent COX-inhibition by 4-MAA (EC50 0.69 ± 0.27 µM) compared with naproxen (EC50 0.034 ± 0.033 µM).Conclusions: Short term treatment with metamizole or naproxen has no significant effect on renal function in moderately sodium depleted healthy subjects. At clinically relevant doses, 4-MAA and naproxen both inhibit COX-mediated renal prostacyclin synthesis.

scholarly journals SP736CCR4HIGHCD4+ CELL POPULATIONS IN KIDNEY GRAFT BLOOD AFTER STEROID WITHDRAWAL: A PROSPECTIVE, RANDOMIZED, CONTROLLED, PARALLEL GROUP STUDY. PRELIMINARY RESULTS

2017 ◽  
Vol 32 (suppl_3) ◽  
pp. iii390-iii390
Author(s):  
Juana Alonso-Titos ◽  
Pedro Ruiz-Esteban ◽  
Eulalia Palma ◽  
Abelardo Caballero ◽  
Veronica Lopez ◽  
...  
Keyword(s):  
Cell Populations ◽  
Kidney Graft ◽  
Steroid Withdrawal ◽  
Preliminary Results ◽  
Randomized Controlled ◽  
Parallel Group Study ◽  
Parallel Group

scholarly journals Absence of age and gender effects on the pharmacokinetics of a single 500-milligram oral dose of levofloxacin in healthy subjects.

1997 ◽  
Vol 41 (7) ◽  
pp. 1562-1565 ◽  
Author(s):  
S C Chien ◽  
A T Chow ◽  
J Natarajan ◽  
R R Williams ◽  
F A Wong ◽  
...  
Keyword(s):  
Renal Function ◽  
Healthy Subjects ◽  
Age Groups ◽  
The Elderly ◽  
Gender Effects ◽  
Pharmacokinetic Parameters ◽  
Age And Gender ◽  
Male And Female ◽  
Young Males ◽  
And Gender

The influence of age and gender on the pharmacokinetics of levofloxacin in healthy subjects receiving a single oral 500-mg dose of levofloxacin was investigated in this parallel design study. Six young males (aged 18 to 40 years), six elderly males (aged > or = 65 years), six young females (aged 18 to 40 years), and six elderly females (aged > or = 65 years) were enrolled and completed the study. The study reveals that the bioavailability (rate and extent) of levofloxacin was not affected by either age or gender. In both age (young and elderly) and gender (male and female) groups of subjects, peak concentrations in plasma were reached at approximately 1.5 h after dosing; renal clearance of levofloxacin accounted for approximately 77% of total body clearance, and approximately 76% of the administered dose was recovered unchanged in urine over the 36 h of collection. The apparent differences in the calculated pharmacokinetic parameters for levofloxacin between the age groups (young versus elderly) and between the gender groups (males versus females) could be explained by differences in renal function among the subjects. A single dose of 500 mg of levofloxacin administered orally to both young and old, male and female healthy subjects was found to be safe and well tolerated. As the differences in levofloxacin kinetics between the young and the elderly or the males and the females are limited and are mainly related to the renal function of the subjects, dose adjustment based on age or gender alone is not necessary.

scholarly journals A randomised, single-blind, single-dose, three-arm, parallel-group study in healthy subjects to demonstrate pharmacokinetic equivalence of ABP 501 and adalimumab

2016 ◽  
Vol 76 (3) ◽  
pp. 526-533 ◽  
Author(s):  
Primal Kaur ◽  
Vincent Chow ◽  
Nan Zhang ◽  
Michael Moxness ◽  
Arunan Kaliyaperumal ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Subjects ◽  
Study Groups ◽  
Time Curve ◽  
End Points ◽  
Parallel Group Study ◽  
Parallel Group ◽  
The Usa ◽  
Abp 501 ◽  
Single Blind

ObjectiveTo demonstrate pharmacokinetic (PK) similarity of biosimilar candidate ABP 501 relative to adalimumab reference product from the USA and European Union (EU) and evaluate safety, tolerability and immunogenicity of ABP 501.MethodsRandomised, single-blind, single-dose, three-arm, parallel-group study; healthy subjects were randomised to receive ABP 501 (n=67), adalimumab (USA) (n=69) or adalimumab (EU) (n=67) 40 mg subcutaneously. Primary end points were area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf) and the maximum observed concentration (Cmax). Secondary end points included safety and immunogenicity.ResultsAUCinf and Cmax were similar across the three groups. Geometrical mean ratio (GMR) of AUCinf was 1.11 between ABP 501 and adalimumab (USA), and 1.04 between ABP 501 and adalimumab (EU). GMR of Cmax was 1.04 between ABP 501 and adalimumab (USA) and 0.96 between ABP 501 and adalimumab (EU). The 90% CIs for the GMRs of AUCinf and Cmax were within the prespecified standard PK equivalence criteria of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and were reported for 35.8%, 24.6% and 41.8% of subjects in the ABP 501, adalimumab (USA) and adalimumab (EU) groups; incidence of antidrug antibodies (ADAbs) was similar among the study groups.ConclusionsResults of this study demonstrated PK similarity of ABP 501 with adalimumab (USA) and adalimumab (EU) after a single 40-mg subcutaneous injection. No new safety signals with ABP 501 were identified. The safety and tolerability of ABP 501 was similar to the reference products, and similar ADAb rates were observed across the three groups.Trial registration numberEudraCT number 2012-000785-37; Results.

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