Browsing by Author "Smit, B. J."

Now showing 1 - 5 of 5
  • Thumbnail Image
    Item
    Cost of breast preservation surgery for cancer
    (Health & Medical Publishing Group, 1992) Smit, B. J.; Liebenberg, T. J.; Du Toit, D. F.
    [No abstract available]
  • Thumbnail Image
    Item
    Morphine and chronic cancer pain
    (Health & Medical Publishing Group, 2001-10) Smit, B. J.
    Cancer pain can be broken down into the following categories: (i),pain caused by the cancer process itself, i.e. bony invasion or nerve compression or infiltration that is likely to present with the features of acute pain; (ii) pain arising from the treatment for the cancer process and likely to present as chronic pain - this might include pain resulting from radical surgery, chemotherapy or radiation therapy; and (hi) bedsores, chronic infection or constipation, which may become part of the pain syndrome.
  • Thumbnail Image
    Item
    Morphine for cancer pain
    (Health & Medical Publishing Group, 1994) Smit, B. J.
    [No abstract available]
  • Thumbnail Image
    Item
    The pharmacokinetic behaviour of hypoxoside taken orally by patients with lung cancer in a phase I trial
    (Health & Medical Publishing Group, 1995) Albrecht, C. F.; Kruger, P. B.; Smit, B. J.; Freestone, M.; Gouws, L.; Miller, R.; Van Jaarsveld, P. P.
    Objective. To study the pharmacokinetic behaviour of hypoxoside taken orally by 24 patients with lung cancer. Design. Randomised open study with three single doses of 1 600, 2 400 and 3 200 mg standardised Hypoxis plant extract (200 mg capsules) and a multiple-dose. study on the first 6 patients taking 4 capsules 3 times daily for 11 days. Participants and setting. Patients with histologically proven squamous, large-cell or adenocarcinoma were hospitalised at the Radiation Oncology Ward, Karl Bremer Hospital, Bellville, W Cape. Methods. Blood was drawn at regular intervals up to 75 hours after single doses and the concentrations of metabolites of the aglucone of hypoxoside, rooperol, were measured with a high-performance liquid chromatography method. For the multiple-dose study blood was drawn before the first dose each day. Concentration-time relationships were analysed according to a conventional single open-compartment model and also by using the NONMEM digital computer programme. Results. Neither hypoxoside nor rooperol appear in circulation. This is due to complete phase II biotransformation to diglucuronide, disulphate and mixed glucuronide-sulphate metabolites, of which the latter is the major component. Considerable interpatient variation in concentration-time relationships was found in the singledose studies. It was due to an active enterohepatic recirculation in some patients and a distinct lag phase in others together with zero-order rate of formation of rooperol in the colon. Computer modelling indicated a single open-compartment model in which the mass of the patient did not influence volume of distribution and clearance because formation of the metabolites is dependent on the metabolising capacity of the patient. However, the elimination of the metabolites follows first-order kinetics with half-lives ranging from 50 hours for the major metabolite to 20 hours for the two minor metabolites. Multiple-dose studies also showed large interpatient variation. Conclusion. In order to reach metabolite levels near 100 μg/ml, which have been shown to be tumouricidal after enzymatic deconjugation to rooperol, maintenance doses need to be individualised for each patient. For most patients, however, a daily dose of 2 400 mg was sufficient.
  • Thumbnail Image
    Item
    A phase I trial of hypoxoside as an oral prodrug for cancer therapy : absence of toxicity
    (Health & Medical Publishing Group, 1995) Smit, B. J.; Albrecht, C. F.; Liebenberg, R. W.; Kruger, P. B.; Freestone, M.; Gouws, L.; Theron, E.; Bouic, P. J. D.; Etsebeth, S.; Van Jaarsveld, P. P.
    Objective. To assess the toxicity of hypoxoside taken orally by 24 patients with lung cancer. Design. Open study with patients taking 1 200 - 3 200 mg standardised Hypoxis plant extract (200 mg capsules) per day divided in 3 doses in order to maintain metabolite blood levels near 100 μg/ml. Participants and setting. Patients with histologically proven squamous, large-cell or adenocarcinoma were hospitalised initially at the radiation oncology ward, Karl Bremer Hospital, Bellville, W. Cape. Thereafter they returned every 2 weeks for full clinical examinations. Methods. Routine biochemical and haematological measurements were done. Patients underwent regular full clinical examinations including radiographs and computed tomography scanning according to the discretion of the principal investigator. Results. Nineteen patients on hypoxoside therapy survived for an average of 4 months with progression of their primary tumours and metastases, while 5 survived for more than a year. One of them survived for 5 years and histological examination of the primary lesion showed absence of cancer. No toxic effects, in clinical examinations or biochemical or haematological measurements, were found that could be ascribed to the ingestion of hypoxoside. Only one occasion of possible drug intolerance, with anxiety, nausea, vomiting and diarrhoea, was noted. Conclusion. The absence of toxicity warrants further investigation of hypoxoside as an oral prodrug, especially in patients with slow-growing necrotising tumours that are inoperable and have high concentrations of β-glucuronidase and sulphatase as high sensitivity for rooperol.