Comparative bioavailability and kinetics of folinic acid in the pharmaceutical formulations of Rescuvolin® and Ledervorin® in healthy volunteers

1988 ◽  
Vol 9 (1) ◽  
pp. 31-39 ◽  
Author(s):  
P. J. M. Guelen ◽  
T. B. Vree ◽  
D. De Vos ◽  
K. Lamers
1989 ◽  
Vol 64 (5) ◽  
pp. 412-416 ◽  
Author(s):  
Jan Bonde ◽  
Niels Melchior Jensen ◽  
Lars E. Pedersen ◽  
Helle R. Angelo ◽  
Seren N. Rasmussen ◽  
...  

2019 ◽  
Vol 220 (6) ◽  
pp. 1044-1048 ◽  
Author(s):  
Marie-Astrid Hoogerwerf ◽  
Luc E Coffeng ◽  
Eric A T Brienen ◽  
Jacqueline J Janse ◽  
Marijke C C Langenberg ◽  
...  

Abstract Four healthy volunteers were infected with 50 Necator americanus infective larvae (L3) in a controlled human hookworm infection trial and followed for 52 weeks. The kinetics of fecal egg counts in volunteers was assessed with Bayesian multilevel analysis, which revealed an increase between weeks 7 and 13, followed by an egg density plateau of about 1000 eggs/g of feces. Variation in egg counts was minimal between same-day measurements but varied considerably between days, particularly during the plateau phase. These analyses pave the way for the controlled human hookworm model to accelerate drug and vaccine efficacy studies.


2010 ◽  
Vol 112 (6) ◽  
pp. 1417-1427 ◽  
Author(s):  
Erik Olofsen ◽  
Eveline van Dorp ◽  
Luc Teppema ◽  
Leon Aarts ◽  
Terry W. Smith ◽  
...  

Background Opioid-induced respiratory depression is antagonized effectively by the competitive opioid receptor antagonist naloxone. However, to fully understand the complex opioid agonist-antagonist interaction, the effects of various naloxone doses on morphine and morphine-6-glucuronide (M6G)-induced respiratory depression were studied in healthy volunteers. Methods Twenty-four subjects received 0.15 mg/kg morphine intravenously at t = 0 followed by placebo, 200 or 400 microg naloxone at t = 30 min. Thirty-two subjects received 0.3 mg/kg M6G intravenously at t = 0 followed by placebo, 25, 100, or 400 microg naloxone at t = 55 min. There were a total of 8 subjects per treatment group. Respiration was measured on a breath-to-breath basis at constant end-tidal Pco2. A mechanism-based pharmacokinetic-pharmacodynamic model consisting of a part describing biophase equilibration and a part describing receptor association-dissociation kinetics was used to analyze the data. Results Naloxone reversal of M6G-induced respiratory depression developed more slowly than reversal of the respiratory effect of morphine. A simulation study revealed that this was related to the slower receptor association-dissociation kinetics of M6G (koff M6G = 0.0327 +/- 0.00455 min versus morphine 0.138 +/- 0.0148 min; values are typical +/-SE). Duration of naloxone reversal was longer for M6G. This was related to the three- to fourfold greater potency of naloxone as an antagonist against M6G compared with morphine. Increasing the naloxone dose had no effect on the speed of reversal, but it did extend reversal duration. Conclusions Naloxone reversal of the opioid effect is dependent on the receptor association-dissociation kinetics of the opioid that needs reversal with respect to the rate of reversal. The pharmacodynamics of naloxone determines reversal magnitude and duration.


2003 ◽  
Vol 64 (7) ◽  
pp. 401-411 ◽  
Author(s):  
Antonio Portolés ◽  
Miguel Puerro ◽  
Ana Terleira ◽  
Angel Rodrı́guez ◽  
Maria-Cruz Caturla ◽  
...  

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