ORG 10172 is a heparinoid with mean molecular weight 6500 daltons. Intravenous bolus injections of ORG 10172 were compared with placebo and heparin injections in 91 separate studies in 83 healthy male subjects. 6400 units ORG 10172 produced a mean maximum change of 14.7 s in kaolin cephalin time (c.f. greater than 120 s for 5000 units heparin). Changes in prothrombin time were minimal (1.6 s for 6400 units ORG 10172 and 4.5 s after 5000 units heparin). A dose‐related increase in bleeding time occurred after ORG 10172 and at high doses (greater than 3200 units) some secondary bleeding, which was never serious, occurred at between 1 and 4 h after incision. A dose‐dependent reduction in ex vivo platelet adhesiveness was found at 10 min after ORG 10172 injection. ORG 10172 promoted a much smaller release of lipoprotein lipase as compared with heparin. The effect of ORG 10172 on plasma factor Xa activity (one measure of its action) was described by a biexponential decay with a mean distribution half‐life of 2.34 (s.e. mean 0.16) h and mean disposition half‐life of 17.6 (s.e. mean 1.1) h. It thus has a much longer duration of effect than heparin. There was a linear relationship of plasma anti‐Xa response to increasing dose although there was some variability only partly explained by differences in body weight or surface area. ORG 10172 administration by bolus intravenous injection was well tolerated and there was no evidence of adverse effects on clinical chemistry or haematology tests.

Nandrolone decanoate (Deca-Durabolin\s=r\) was injected intramuscularly into healthy volunteers. One group of females received one injection of 100 mg and three groups of males received one injection of 200 mg, two repeat injections of 100 mg or four repeat injections of 50 mg respectively. The serum levels of nandrolone (19-nortestosterone) were determined by

In fitting the one-compartment open model with first-order processes to empirical data, it has frequently been found for single-dose administration that the absorption and elimination rate constants approach each other. If these rate constants tend to be equal, such combinations are impossible to solve with the general model equation. In 1968, Dost published a special model function by which the problems associated with the general model function can be circumvented. No solution, however, has been published for multiple-dose functions with the one-compartment model in which the absorption and elimination rate constants are equal. For a two-compartment open model with first-order processes, similar problems arise if the absorption and exponential distribution rate constants approach each other. Although this type of problems is often encountered in pharmacokinetic curve-fitting to empirical data, no exact solution has been published. Equations are given for multiple-dose administration with the one-compartment open model in which the absorption and elimination rate constants are equal, and for single-dose and multiple-dose administration with the two-compartment open model in which the absorption and exponential distribution rate constants are equal. Included are criteria to decide whether the new or the classical model functions should be applied in the case of a two-compartment open model.

No abstract

1. In a cross-over study a new low molecular weight heparinoid Org 10172 was administered to 12 elderly male and female volunteers. It was well tolerated and no adverse effects occurred. 2. The absolute bioavailability of Org 10172 as measured by plasma anti-Xa activity, glycosaminoglycuronans with no affinity to antithrombin III (NoA-GAG) and thrombin generation inhibiting activity approached 100% in both sexes. 3. The half-life of elimination of its anti-Xa activity (19.2 +/- 6.1 h) was similar to that found previously in young volunteers. Org 10172 was further characterised by a rapid disappearance from the circulation of its anti-thrombin activity (t1/2 1.8 +/- 0.6 h) and of the NoA-GAG (t1/2 3.5 +/- 2.1 h). 4. Its thrombin generation inhibiting activity was of intermediate duration (t1/2 elimination 6.2 +/- 4.0 h).