Weight, pregnancy and oral contraceptives affect intravenous paracetamol clearance in young women.

OBJECTIVES: Because of the extensive variability in paracetamol clearance in young women, published data were pooled with newly collected observations in search of covariates of paracetamol pharmacokinetics (PK) within this specific population. SUBJECTS AND METHODS: PK estimates and clinical characteristics [pregnant, weight, exposure to oral contraceptives (OC)] in young women following IV loading dose (2 g paracetamol) were pooled, using a non-compartmental linear disposition model in individual time-concentration profiles. Data were reported by median and range. Rank correlation was used to link clearance (l/h) to weight, Mann Whitney U test to compare clearance (l/h.m-2) between subgroups (pregnant, OC exposure). Finally, a multiple regression model with clearance (l/h) in all women and all non-pregnant women was performed. RESULTS: Based on 73 paracetamol PK estimates, a 8-fold variability in clearance (range 7.1-62.2 l/h) was documented, in part explained by a correlation (r2=0.36) between clearance (l/h) and weight. Clearance (l/h and l/h.m-2) and distribution volume (l) at delivery (n=36) were higher compared to non-pregnant observations. In non-pregnant women, women on OC (n=20) had a higher paracetamol clearance (l/h.m-2) compared to women (n=17) not on OC (p = 0.023). Weight (p = 0.0043) and pregnancy (p = 0.02) were independent variables (r=0.56) of paracetamol clearance (l/h). In non-pregnant women, weight (p = 0.009) and OC exposure (p = 0.03) were independent variables (r=0.51). CONCLUSIONS: Weight, pregnancy and OC result in higher clearance of IV paracetamol in young women. Besides compound specific relevance, these findings also unveil covariates of drug metabolism in young women.

Animal model of thermal injuries.

Experimental studies of burns require the use of different animal models with the aim to imitate and reproduce pathophysiological conditions. The aim of this work was to establish experimental model of thermal injury. New Zealand rabbits, weighted from 1.8 kg to 2.3 kg, were utilised during our study. Another, also utilized, animal types were laboratory Rattus rats, species Wistar, albino type, females with body weight of about 232 g. All animals were from our own litter (Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine in Sarajevo). During the experiment, animal were properly situated in adequate cages and rooms, at the controlled temperature (22 +/- 2 degrees C), and in the air with normal humidity level. All animals took food and water ad libitum. Rabbits received anesthesia--intravenous pentobarbital sodium in a dose of 60 mg/kg, and then, hair from the upper side of the each rabbit ear was removed and burns were caused by a metal seal in the same manner as in rats. Rats were primarily anesthesied by intraperitoneal pentobarbital sodium in a dose of 35 mg/kg, and then, their hair was removed from the scapula zone (5 cm x 5 cm). Burns were caused by contact with a round metal seal, heated at 80 degrees C in a water bath, during the period of 14 seconds together with contact thermometer control. Round metal seal (radius: 2.5 cm; weight: 100 g; surface: 5 cm2) was just placed on the rat skin without any additional pressure. In order to maintain the microcirculation in the burn wound and to reduce the conversion of partial-thickness skin burns to the burns of the full-thickness skin, all burn wounds were immediately sunk in the 4 degrees C water. Subsequent to that procedure, all animals were individually situated in the proper cages, and left to rest for 4 hours with a constant cautious monitoring of the wound development and animal general state.

[On the occasion of 50 years of the Medical School in Sarajevo]. / Povodom pedeset godina medicinskog fakulteta u Sarajevu.

This year it has been 50 years since the Medical Faculty in Sarajevo was founded. Half a century in existence of a scientific and educational institution represents a period which is sufficient to make a serious retrospective, but also to make a serious analysis and projections for the future. Medical Faculty in Sarajevo was therefore been opened in 1944. There were students in the first generation, who completed the educational process from the first year program of studies. Due to circumstances of war this process at the Faculty was interrupted. On November 16, 1946, Medical Faculty in Sarajevo was reopened and since then it has been continuously working for 48 years, maintaining its educational, scientific and health activities. Former departments of the General Hospital in Sarajevo have grown into its clinical departments and during the period between 1947 until 1952, the majority of its institutes have been already constructed. The development of some of the clinics was however a little bit slower. Within the educational process we can separate four stages in the development of the Faculty: period from 1954 which has been characterized by a classical middle-european educational plan and program; from 1954-1956, the so-called "block system" of mono-course educational process; in the period 1956-1990, a five years study curriculum has been promoted with attempts to reform the educational process; from 1990 until today, the six-years study curriculum has been introduced, being in accordance with the plans and programs of European educational institutions.(ABSTRACT TRUNCATED AT 250 WORDS)

[The effect of vasodilators on isolated smooth muscle]. / Uticaj vazodilatatora na izolirane glatke misice.

Bencyclane (Fludilat), Metamizol (Novalgetol) and Xanthinol nicotinate (Complamin) and their combination were considered as relaxators of smooth muscle. The smooth muscles were isolated from stomach, urinary bladder, oesophagus, vas deferens and aorta of rats. The electrical stimulations induced contractions. The mixture of vasodilators decreased the tonus and induced contractions. The single vasodilators increased tonus and induced spasm sometimes.