EXTRAHEPATIC FIRST-PASS METABOLISM OF NIFEDIPINE IN THE RAT

The peroral (po) bioavailability of nifedipine is reported to range from about 45 to 58% in the rat; this compares favourably to human beings. The metabolism of nifedipine is similar in rats and humans (oxidation of the dihydropyridine ring), with the liver believed to be solely responsible for the systemic clearance of the drug and the observed first-pass effect after po dosing. The purpose of this study was to determine whether intestinal metabolism also contributes to the first-pass elimination of nifedipine in the rat. The systemic availabilities of nifedipine doses given by po, intracolonic (ic), and intraperitoneal (ip) routes of administration were compared to that for an intravenous (iv) dose (in each case a dose of 6 mg kg⁻¹ was given) using adult male Sprague–Dawley rats (249–311 g, n =6 or 7/group). The geometric mean of systemic nifedipine plasma clearance after iv dosing was 10·3 mL min⁻¹ kg⁻¹. The nifedipine blood-to-plasma ratio was found to be about 0·59. Therefore, the systemic blood clearance of nifedipine was about 17·5 mL min⁻¹ kg⁻¹; which, compared to the hepatic blood flow of rats (55 to 80 mL min⁻¹ kg⁻¹) showed that nifedipine is poorly extracted by the liver (0·22≤E_H≤0·32). The mean absolute bioavailabilities of the po, ip, and ic doses were 61, 90, and 100%, respectively. Assuming complete absorption of the extravascular nifedipine doses these results indicate that, in addition to hepatic extraction, substantial first-pass elimination of nifedipine occurs within the wall of the small intestine but not the colon of the rat. © 1997 John Wiley & Sons, Ltd.     

C-erb B-2 STAINING IN PRIMARY SYNOVIAL CHONDROMATOSIS: A COMPARISON WITH OTHER CARTILAGINOUS TUMOURS

In this study C-erb B-2 immunostaining has been used to highlight distinct differences between the cartilage found in primary synovial chondromatosis ( n =20), normal articular cartilage ( n =10), benign enchondromas ( n =10), and chondrosarcomas ( n =10). There was no positive staining in either the normal cartilage or the chondromas, but 15 cases of synovial chondromatosis showed at least some staining, although in the majority of cases fewer than 50 per cent of cells stained positive. There was no correlation between cellularity/pleomorphism and the extent or intensity of staining. Five of the chondrosarcomas were positive, with more than 50 per cent of cells showing positive staining in three of these cases. All positive cases in this series showed a diffuse cytoplasmic staining pattern. Despite these results, there was no Ki-67 positive staining in synovial chondromatosis, which tends to suggest that the demonstrated expression of C-erb B-2 is not related to proliferative activity. The significance of this staining remains undetermined.     

THE TREATMENT OF SICCA FEATURES IN SJOGREN'S SYNDROME: A CLINICAL REVIEW

Patients with SS often suffer considerable distress due to siccasymptoms and the complications of mucosal dryness. Althoughthere are many topical treatments available, the literatureon their use is scant. This paper describes the treatments availableand suggests a rationale for the choice of product. KEY WORDS: Sjögren's syndrome, Keratoconjunctivitis sicca, Xerostomia, Treatment, Therapeutics, Guidelines     

Cyclic changes in composition and volume of the breast during the menstrual cycle, measured by magnetic resonance imaging

Summary. The volumes and spin-lattice (T₁) relaxation times of breast tissues and parenchymal water content were measured non-invasively by magnetic resonance imaging (MRI) in eight healthy women during four to eight consecutive menstrual cycles. Total breast volume, and parenchymal volume, T₁ relaxation time and water content were lowest between days 6 and 15. Between days 16 and 28, parenchymal volume, T₁ relaxation time and water content rose sharply by 38·9%, 15·1% and 24·5%, respectively, and peaked after day 25. Within 5 days of the onset of menses, parenchymal volume fell sharply by 30·3%, while water content declined by 17·5%. Rising parenchymal volume in the second half of the menstrual cycle is not solely due to increased tissue water content and provides in vivo evidence for both growth and increased tissue fluid at this time.