Summary
Pharmacokinetic studies of 1,3,3,5,5 pentakis (aciridino)-1λ6,2,4,6,3λ5,5λ5 thiatriazadiphosphorine-1-oxide (‘SOAz’), a new antineoplastic agent containing an inorganic ring system and five aziridino groups, were performed in six patients who took part in a phase I clinical trial of the agent. The drug was administered as a rapid IV infusion. Serum decay curves could be fitted to an open two-compartment model of drug disappearance. After a short initial phase with a t1/2 (±SD) of 7.8±4.2 min a terminal phase with a dose-independent half-life of 203±17 min occurred. The coefficient of apparent distribution was 0.71±0.13. The renal clearance was 75±11 ml/min and the total body clearance 162±23 ml/min. A percentage of 46.5±6.6 of the administered drug could be recovered unchanged in the urine within 24 h. It is concluded that in view of concentrations known to be effective in vitro, administration in large single doses may be advantageous. Dose adjustments should be made for patients with impaired renal function.
Similar content being viewed by others
References
Baalmann HH, Velvis HP, van de Grampel JC (1972) The preparation of a new inorganic ring system containing one sulfur, two phosphorus and three nitrogen atoms in the ring. Recueil des Travaux Chimiques 91:935
Beneken genaamd Kolmer MH, Rodenhuis S, van de Grampel JC, Uges DRA (1983) Determination of the antitumor agent SOAz by a gaschromatographic assay suitable for pharmacokinetic studies in man. Cancer Chemother Pharmacol 10:170–173
Boxenbaum HG, Riegelman S, Elashoff RM (1974) Statistical estimations in pharmacokinetics. J Pharmacokinet Biopharm 2:123
Greenblatt DJ, Koch Weser J (1975) Drug therapy. Clinical pharmacokinetics. I. N Engl J Med 293:702
Guerch G, Labarre JF, Sournies F, Manfait M, Spreafico F, Filippeschi S (1982) The antineoplastic activity of 2,2,4,4 tetrakis (aziridinyl)-6,6-dichlorocyclotriphosphaza-1,3,5-triene, gem-N3P3Az4Cl2, a novel anticancer agent. Inorg Chim Acta 66:175
Labarre JF, Sournies F, Cros S, François G, van de Grampel JC, van der Huizen AA (1981) New designs in inorganic ring systems as anticancer drugs. Antitumor activity of the aziridino (ethylene-imino) derivatives (NPAz2)2NSOX with X=F, Az, Ph. Cancer Lett 12:245
Loo JCK, Riegelman S (1970) Assessment of pharmacokinetic constants from postinfusion blood curves obtained after i.v. infusion. J Pharm Sci 59:53
Ritchel WA (1980) Handbook of basic pharmacokinetics, 2nd ed. Drug Intelligence Publications, Hamilton
Rodenhuis S, Mulder NH, Sleijfer DT, Schraffordt Koops H, van de Grampel JC (1983) Phase I clinical trial of (NPAz2)2NSOAz: ‘SOAz’. Cancer Chemother Pharmacol 10:178–181
Van de Grampel JC, van der Huizen AA, Jekel AP, Wiedijk D, Labarre JF, Sournies F (1981) Derivatives of cis-NPCl2(NSOCl)2 and (NPCl2)2NSOCl. XVI. The preparation of some aziridino (ethylene-imino) derivatives of (NPCl2)2NSOX (X=F, Az, Ph) with a potential anticancer activity. Inorg Chim Acta 53:L169
Wheeler GP (1975) Mechanism of action of nitrosureas. In: Sartorelli AC, Johns DG (eds) Antineoplastic and immunosuppressive agents, part II. Springer, Berlin Heidelberg New York, p 65
Author information
Authors and Affiliations
Additional information
SOAz, 1,3,3,5,5 pentakis (aciridino)-1λ6,2,4,6,3λ5,5λ5 thiatriazadiphosphorine-1-oxide
Rights and permissions
About this article
Cite this article
Rodenhuis, S., Scaf, A.H.J., Mulder, N.H. et al. Clinical pharmacokinetics of (NPAz2)2NSOAz: ‘SOAz’. Cancer Chemother. Pharmacol. 10, 174–177 (1983). https://doi.org/10.1007/BF00255756
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00255756