Introduction to Slam II/sup R/ and Slamsystem/sup R/

Abstract

SLAM 11 is a general-purpose language which has been used since 1979 to model a wide variety of systems: manufacturing operations, transportation systems, communication networks, computer systems, military operations and material handling systems, just to name a few. Experience with these applications, plus development in simulation research, have led to the expansion of the language throughout its lifetime. The ease of using the SLAM I1 language was greatly increased by the introduction of SLAMSYSTEM in 1988; SLAMSYSTEM Version 4.0 isthemostrecentrelease,arrivingin 1993. SLAMSYSTEM is an integrated simulation system based on the Microsoft Windows interface (under MS-DOS) or the OS/2 Presentation Manager. This tutorial will demonstrate the process of building, analyzing, and presenting SLAM I1 simulation models using SLAMSYSTEM.

Phenylbutazone-warfarin interaction in the dog

“…A nearly four-fold difference exists in the free fraction of warfarin in human and dog plasmas when determined by ultrafiltration (Bachmann, 1974). This difference is in good agreement with the relative differences in warfarin binding constants for human and dog albumin (O'Reilly, 1970), and may contribute to the shorter plasma half-life and apparently greater sensitivity of the dog to the hypoprothrombinaemic effect of warfarin compared to man. The normal value for the free warfarin fraction over the therapeutic range of warfarin plasma concentration in man is 0.6.x This value can be increased to 1.0% with relatively small concentrations of phenylbutazone (40 pg ml-l) (Bachmann, 1974).…”

Effects of Phenylbutazone, Tolbutamide, and Clofibric Acid on Binding of Racemic Warfarin and Its Enantiomers to Human Serum Albumin

“…In the present investigation, the binding behavior of the isomers with human serum albumin was characterized by equilibrium dialysis to determine if there is a correlation between the free fraction of the isomers in uitro and clinically observed elimination kinetics. In two studies (9, lo), the S(-)-isomer had a significantly higher affinity for the primary site; in two other studies (11,12), no significant differences in isomer binding were found.…”

Improved parameter estimates in drug-protein binding studies by non-linear regression

“…There is n good deal of variation between different workers on supposedly similar systems, and inspection of the data suggested that choice of treatment could be responsible in part. For example, consider the bishydroxycoumarin-human plasma albumin interaction where Chignell(l970) reported the number of sites in the highest affinity class (n3 as 3 and an association constant (K,) of 7.7 x lo5 M-,; Garten & Wosilait (1971) found n, = 2.08 and K, = 2.08 x lo6 M -~; O'Reilly (1971) gave n, = 2-0 f 0.1 and K , = 2.31 3 0.05 x lo5 M-, and Cho, Mitchell & Pernarowski (1971) gave n, = 3 and K , = 3.5 x 105 M-1.…”