Drug Evaluation, Preclinical/*methods ; Statistics

In calculating pharmacokinetic parameters, Subjective bias may be induced by using the method of residuals. This paper reports a nonlinear least squares fitting program which may be adapted in APPLE II microcomputer. The program can not only increase the precision of estimated parameters, but also provide objective criteria e.g. Akaike's Information Criterion ( AIC ) for determining which kind of compartment model is most appropriate. Furthermore, the standard error of parameter is calculated which gives the variability of the estimation. The use of this program is guided on-screen prompts that display Some form of menu including the various types of compartmental models for intra and extravascular administration. The data can be stored or drawn out from the disk and the plot of curve fitting is readily feasible.

AIM: To analyse quantitatively the interactions among ethanol, chloral hydrate and naloxone with isobologram, Q-test and multiple logistic regression methods. METHODS: The hypnotic effects of the three drugs on Kunming mice were observed. In two drugs interaction study, chloral hydrate and ethanol were given at different ratios (25∶75, 50∶50, 78∶22 and 80∶20). In three drugs interactions study, 15 min after treatment of naloxone at fixed dose (0.5 mg*kg-1 and 0.2 mg*kg-1) the mixture of chloral hydrate and ethanol (at 1∶1 and 1∶3 ratio) was given to induce sleep. The ED50 for hypnotic action (righting reflex loss) of chloral hydrate, ethanol, naloxone and their mixtures were calculated by use of isobologram, interaction Q-index test and multivariate logistic regression analysis. RESULTS: The mixtures of ethanol and chloral hydrate in all ratios revealed partial but significant synergism. But in addition with naloxone the three agents showed different natures of interactions according to different naloxone levels. CONCLUSION: There are synergistic interactions in hypnotic ED50s between ethanol and chloral hydrate at different ratios and antagonistic interaction in adding a fixed dose of naloxone. The results coincide with the pharmacologistic mechanism discussed in this paper.