caa a22 4500 465789439 CHVBK 20180323112019.0 cr unu---uuuuu 170327e19900201xx s 000 0 eng 10.1007/BF00216921 doi (NATIONALLICENCE)springer-10.1007/BF00216921 Pharmacokinetics of the antitumor antibiotic n-pentyl-sparsomycin in beagle dogs [Elektronische Daten] [Zbigniew Zylicz, D. Wagener, Marina Garzotto, Tom Vree, Eppo van der Kleijn, Leon van den Broek, Harry Ottenheijm] Summary: N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 β was 0.2 hours (12 minutes) and t1/2 τ was 0.75 ± 0.1 hours (45 ± 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 τ was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics. Kluwer Academic Publishers, 1990 sparsomycin nationallicence n-pentyl-sparsomycin nationallicence pharmacokinetics nationallicence beagle dogs nationallicence Zylicz Zbigniew Department of Internal Medicine, Division of Medical Oncology, St. Radboud University Hospital, Nijmegen, The Netherlands aut Wagener D. Department of Internal Medicine, Division of Medical Oncology, St. Radboud University Hospital, Nijmegen, The Netherlands aut Garzotto Marina Department of Internal Medicine, Division of Medical Oncology, St. Radboud University Hospital, Nijmegen, The Netherlands aut Vree Tom Department of Clinical Pharmacy, St. Radboud University Hospital, Nijmegen, The Netherlands aut van der Kleijn Eppo Department of Clinical Pharmacy, St. Radboud University Hospital, Nijmegen, The Netherlands aut van den Broek Leon Department of Organic Chemistry, University of Nijmegen, The Netherlands aut Ottenheijm Harry Organon BV, Oss, The Netherlands aut Investigational New Drugs Kluwer Academic Publishers 8/1(1990-02-01), 25-32 0167-6997 8:1<25 1990 8 10637 https://doi.org/10.1007/BF00216921 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00216921 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zylicz Zbigniew Department of Internal Medicine, Division of Medical Oncology, St. Radboud University Hospital, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Wagener D. Department of Internal Medicine, Division of Medical Oncology, St. Radboud University Hospital, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Garzotto Marina Department of Internal Medicine, Division of Medical Oncology, St. Radboud University Hospital, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Vree Tom Department of Clinical Pharmacy, St. Radboud University Hospital, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- van der Kleijn Eppo Department of Clinical Pharmacy, St. Radboud University Hospital, Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- van den Broek Leon Department of Organic Chemistry, University of Nijmegen, The Netherlands aut NATIONALLICENCE 700 1- Ottenheijm Harry Organon BV, Oss, The Netherlands aut NATIONALLICENCE 773 0- Investigational New Drugs Kluwer Academic Publishers 8/1(1990-02-01), 25-32 0167-6997 8:1<25 1990 8 10637 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer