ABSTRACT
Compartment model and statistical moment model are important theories of pharmacokinetics. However, they have obvious limitations due to the influence of drug distribution. Sometimes, the demarcation point between the distribution phase and the elimination phase of the compartment model is difficult to determine, which results in inconvenience for its application. The nature of zero order moment, AUC of statistical moment model, is blood drug concentration, but not drug amount in the body. For drugs of two-compartment or multi-compartment models, the results reflect alterations in blood drug concentration, not necessarily changes in the amount of drug in the body. In the slow and steady intravenous drip, the drug distribution in the body is basically balanced, and the alteration of blood drug concentration can reflect the alteration of drug amount in the body. Over 5 half-life, the blood drug concentration basically reaches a stable status. And the alteration of the blood drug concentration only reflects the drug elimination. For first-order kinetic drugs, the elimination rate constant (K) can be calculated by linear regression according to the elimination rule (lnC=lnC0-Kt). And then, the half-life (t1/2), the amount of drug in the body, the apparent distribution volume (Vd), and the clearance rate (CL) can be calculated successively. During slow and constant velocity intravenous dripping, drug amount is proportional to blood drug concentration in the body. And there is an exponential relationship between the blood drug concentration and time [Ct=C0+(Css-C0) (1-e-Kt)]. The first-order exponential regression is performed between Ct and t to calculate elimination threshold concentration (C0), steady blood drug concentration (Css) and K. Then, t1/2, steady drug amount (Ass), Vd and CL are calculated. The distributed equilibrium model avoids the interference of drug distribution, and is closer to reality.
ABSTRACT
Objective To assess the therapeutic effects of activated charcoal on the acute dichlorvos poisoning in rats. Method Thirty male clean grade Wistar rats were randomly (random number) divided into three groups: control group (group A, n = 10), single dose activated charcoal group (group B, n = 10) and multi-dose activated charcoal (group C, n=10). The rats of group A were suffered from 35 mg/kg dichlorvos exposure by oral without activated charcoal and senna. The rats of group B received 35 mg/kg dichlorvos exposure by oral with 175 mg/kg activated charcoal given immediately after dichlorvos exposure and 35 mg/kg senna given half an hour later. In the group C, 35 mg/kg dichlorvos was given to rats by oral with 175 mg/kg activated charcoal given immediately after dichlorvos exposure and 35 mg/kg senna given half an hour later and then every four hours. Blood samples were collected from the carotid artery at different intervals after exposure. DDVP concentration and total blood acetyl-cholinesterase activity were detected. Differences in serum DDVP concentration, Cmax, AUC (0→∞ ), MRT and acetylcholinesterase among three groups were calculated by using ANOVA. Results Serum DDVP levels in single dose group and in multi-dose group were significantly different from those in control group (P < 0.05). The DDVP levels in multi-dose group were significantly different from those in single dose group 4 hours after exposure (P < 0.05). The AUC and Cmax in activated charcoal treatment groups were significantly different from those in control group (P < 0.05). There were no significant differences in MRT among three groups. Fours hours after exposure to dichlorvos,the levels of serum acetylcholinesterase in rats of group B and group C were significantly different from that in rats of group A (P < 0.05), and there was no significant difference in acetylcholinesteras between group B and group C (P > 0.05). Another four hours later, no differences in acetylcholinesterase were found a-mong three groups (P > 0.05). Conclusions The peak concentrations of dichlorvos in blood are lower in group B and group C, and the blood acetylcholinesterase inhibition is quelled by activated charcoal. Therefore, the effects of multi - dose of activated charcoal is better than that of single dose of activated charcoal.