Correlation of Unbound Plasma Clearances of Fifteen Extensively Metabolized Drugs Between Humans and Rats

Unbound plasma clearances (CLu) in humans and rats of 15 extensively metabolized drugs (phe-nytoin, hexobarbital, pentobarbital, phenylbutazone, warfarin, tolbutamide, valproate, phenobarbital, amobarbital, quinidine, chlorpromazine, propranolol, pentazocin, antipyrine, and diazepam), studied earlier by Sawada et al. (J. Pharmacokin. Biopharm. 13:477–491, 1985), were calculated. It was found that the ratio of CLu per square meter of body surface area between human and rat ranged from 0.38 for pentobarbital to 2.34 for tolbutamide, with a mean ratio of 1.07. When body weight (BW) was used for correlation, the mean CLu was proportional to BW ^{0.657±0.0935}. A rationale for the above empirical findings is postulated. The present study seems to indicate the existence of a general similarity or predictability in the CLu of drugs between rats and humans. Low correlations were generally obtained when total (bound and unbound) plasma clearances were used for comparison.     

Granular cell myoblastoma of the extrahepatic biliary system

We have reported our experience with two cases of granular cell myoblastoma, bringing the total number of cases to 29. Granular cell myoblastoma of the extrahepatic biliary system is a rare benign tumor that affects black women predominantly. Both black men in this study had multiple lesions involving the skin and biliary system. Surgery is necessary for tissue diagnosis and curative resection. Tumors involving the common bile duct or common hepatic duct require wide local excision and bilioenteric anastomosis. The cause is uncertain, but present data indicate a neuroectoderm origin.     

11例泌尿生殖相关多原发癌的报告

本文报告我科1985年～1995年间11例与泌尿器官相关的多原发癌。结合文献重点强调多原发癌有别于晚期转移癌,它是人体内同时或异时存在的两种或两种以上各自独立的原发癌,如能及早积极手术治疗辅以其他疗法则其预后不比单原发癌差。并对其发病率、病因及可能的发病机制等进行了讨论。     

Memory function and serotonin transporter promoter gene polymorphism in ecstasy (MDMA) users

Although 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) has been shown to damage brain serotonin (5-HT) neurons in animals and possibly humans, little is known about the long-term consequences of MDMA-induced 5-HT neurotoxic lesions on functions in which 5-HT is involved, such as cognitive function. Because 5-HT transporters play a key element in the regulation of synaptic 5-HT transmission it may be important to control for the potential covariance effect of a polymorphism in the 5-HT transporter promoter gene region (5-HTTLPR) when studying the effects of MDMA as well as cognitive functioning.The aim of the study was to investigate the effects of moderate and heavy MDMA use on cognitive function, as well as the effects of long-term abstention from MDMA, in subjects genotyped for 5-HTTLPR. A second aim of the study was to determine whether these effects differ for females and males. Fifteen moderate MDMA users (<55 lifetime tablets), 22 heavy MDMA+ users (>55 lifetime tablets), 16 ex-MDMA+ users (last tablet > 1 year ago) and 13 controls were compared on a battery of neuropsychological tests. DNA from peripheral nuclear blood cells was genotyped for 5-HTTLPR using standard polymerase chain reaction methods.A significant group effect was observed only on memory function tasks (p = 0.04) but not on reaction times (p = 0.61) or attention/executive functioning (p = 0.59). Heavy and ex-MDMA+ users performed significantly poorer on memory tasks than controls. In contrast, no evidence of memory impairment was observed in moderate MDMA users. No significant effect of 5-HTTLPR or gender was observed.While the use of MDMA in quantities that may be considered "moderate" is not associated with impaired memory functioning, heavy use of MDMA use may lead to long lasting memory impairments. No effect of 5-HTTLPR or gender on memory function or MDMA use was observed.     

THE PHYSIOLOGICAL SIGNIFICANCE OF TOTAL BODY CLEARANCE IN PHARMACOKINETIC STUDIES

The significance of the total body clearance (CL) is studied based on a physiological pharmacokinetic model. In the absence of evidence to the contrary, and for the sake of uniformity, it is proposed that the elimination rate of a drug at any time after various routes of dosing be assumed to be proportional to its systemic arterial plasma (blood) concentration with a proportionality constant equal to CL. The CL, calculated by the intravenous dose divided by the AUC, is defined as the hypothetical volume of the systemic arterial plasma (blood) completely cleared of drug per unit time even though the drug is eliminated by the lungs and venous plasma is assayed. A marked difference in the calculated elimination rate of lidocaine in patients based on arterial or venous plasma data is demonstrated. The calculated CLs which are sometimes greater than the cardiac output can be rationalized. The limitation of conventional multi-compartmental mammillary modelling theory in the defining of CL is discussed.