Browsing by Author "Seifart, H. I."

Now showing 1 - 7 of 7
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    Diffusion of Diclofenac and Piroxicam from commercially available gels through human skin
    (2003) Van der Bijl, P.; Van Eyk, A. D.; Seifart, H. I.; De Jager, R.; Nel, C. M. M.
    No abstract available.
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    Endogenous immunoreactive digitalis-like substance in neonatal serum and placental extracts
    (Health & Medical Publishing Group, 1984) Beyers, A. D.; Spruyt, L. L.; Seifart, H. I.; Kriegler, A.; Parkin, D. P.; Van Jaarsveld, P. P.
    Therapeutic levels of digoxin in the serum of untreated neonates delivered to mothers who had not received the drug prenatally were detected by radio-immunoassay. Digoxin levels in neonates should be interpreted with care because of the unknown contribution by the endogenous digitalis-like substance (DLS) to the level of the drug. Three commercially available radio-immunoassay kits were compared with regard to their sensitivity and reproducibility in detecting the endogenous DLS. The kit from Clinical Assays (Cambridge, Mass., USA) was selected for further investigations. In a series of 35 paired samples of maternal and cord blood the average DLS values in terms of digoxin were 0.52 ± 0.07 and 0.81 ± 0.27 ng/ml respectively. This difference is statistically highly significant. In the case of infants with DLS values of 1-1.5 ng/ml in terms of digoxin, approximately 1 week was required to reach non-therapeutic digoxin levels, i.e. below 0.5 ng/ml. Gel chromatography showed that the DLS in neonatal serum was more closely associated with protein than is authentic digoxin. In placental extracts it followed the elution profile of the protein completely, but it shifted to fractions with a lower molecular weight than haemoglobin after trypsinization. The level of DLS in neonatal serum was also increased by more than half its original value by trypsinization. Proteolysis therefore seems to have a releasing effect on DLS. The molecular size of this substance is probably in the same range as that of polypeptides, since it was not dialysable from trypsinized and untreated samples through a membrane with a 22,000 dalton molecular weight cut-off point.
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    Oligomeric substances in ampicillin preparations : a comparison of Penbritin, Famicillin and Petercillin
    (Health & Medical Publishing Group, 1988) Van der Bijl, P.; Seifart, H. I.; Parkin, D. P.; Mattheyse, F. J.
    An investigation into the presence of potentially harmful oligomers in formulations of ampicillin for parenteral administration available in the RSA was undertaken by means of high-pressure liquid chromatography. Significant differences were found to exist between formulations.
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    'n Oorsig van die bepaling van die vroeë bakterisidiese aktiwiteit van verskeie antituberkilosemiddels
    (AOSIS, 2003) Donald, P. R.; Sirgel, F. A.; Venter, A.; Fourie, P. B.; Parkin, D. P.; Seifart, H. I.; Van de Wal, B. W.; Maritz, J. S.
    The early bactericidal activity (EBA) of an antituberculosis agent is the daily decline in log10 colony forming units of M tuberculosis per ml of sputum during the first two days of treatment with the agent. It reflects the capacity of an agent to kill the actively metabolising organisms in tuberculosis lung cavities. It offers a relatively cheap means to evaluate the antituberculosis activity of an agent in a small group of patients within a matter of months. This article summarizes the authors’ experience in seven published EBA studies and identifies sources of variation in the procedure. The patients who participated in these studies had a mean age of 33 years, a mean weight of 50 kg and there was extensive or massive involvement of the lungs in 55% of patients. The highest EBA values (0,50-0,66) were found in groups of patients receiving isoniazid and the lowest values (0,05 and 0,09 respectively), in patients receiving the aminoglycosides amikacin and paromomycin in a dose of 15 mg/kg body weight. The variation in EBA in 248 patients was 0,0312 and the variation ascribable to the process of sputum production and collection was 0,0233. This implies that the different aspects of sputum production and collection involved in obtaining a representative sputum sample are responsible for most of the variation in EBA results. The selection of patients for inclusion in EBA studies and their ability to co-operate in producing a representative sputum specimen are of critical importance in the successful completion of EBA studies.
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    Permeability of intestinal mucosa to crystalline and tabletted isoniazid (INH)
    (Health & Medical Publishing Group, 2003) Van der Bijl, P.; Seifart, H. I.; Van Eyk, A. D.
    When administered orally, isoniazid (INH), which continues to form the basis of most first-line standard antituberculosis regimens, reaches peak plasma concentrations of 3 - 5 μg/ml within 1 - 2 hours after ingestion of usual doses.1 Various tablet and slow-release matrix forms are available and these processed preparations are most often used clinically. However, various studies undertaken in our Department have shown crystalline INH to produce better blood levels within the first 2 hours after ingestion than the commonly used tabletted form.
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    The pharmacokinetics of enteral antituberculosis drugs in patients requiring intensive care
    (Health and Medical Publishing Group (HMPG), 2013-06) Koegelenberg, C. F. N.; Nortje, A.; Lalla, U.; Enslin, A.; Irusen, E. M.; Rosenkranz, B.; Seifart, H. I.; Bolliger, C. T.
    Background. There is a paucity of data on the pharmacokinetics of fixed-dose combination enteral antituberculosis treatment in critically ill patients. Objectives. To establish the pharmacokinetic profile of a fixed-dose combination of rifampicin, isoniazid, pyrazinamide and ethambutol given according to weight via a nasogastric tube to patients admitted to an intensive care unit (ICU). Methods. We conducted a prospective, observational study on 10 patients (mean age 32 years, 6 male) admitted to an ICU and treated for tuberculosis (TB). Serum concentrations of the drugs were determined at eight predetermined intervals over 24 hours by means of highperformance liquid chromatography. Results. The therapeutic maximum plasma concentration (Cmax) for rifampicin at time to peak concentration was achieved in only 4 patients, whereas 2 did not achieve therapeutic Cmax for isoniazid. No patient reached sub-therapeutic Cmax for pyrazinamide (6 were within and 4 above therapeutic range). Three patients reached sub-therapeutic Cmax for ethambutol, and 6 patients were within and 1 above the therapeutic range. Patients with a sub-therapeutic rifampicin level had a higher mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score (p=0.03) and a lower estimated glomerular filtration rate (GFR) (p=0.03). Conclusions. A fixed-dose combination tablet, crushed and mixed with water, given according to weight via a nasogastric tube to patients with TB admitted to an ICU resulted in sub-therapeutic rifampicin plasma concentrations in the majority of patients, whereas the other drugs had a more favourable pharmacokinetic profile. Patients with a sub-therapeutic rifampicin concentration had a higher APACHE II score and a lower estimated GFR, which may contribute to suboptimal outcomes in critically ill patients. Studies in other settings have reported similar proportions of patients with ‘sub-therapeutic’ rifampicin concentrations.
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    Practical management of therapeutic diphenylhydantoin concentrations in children
    (Health & Medical Publishing Group, 1999) Smit, A.; Schoeman, J. F.; Seifart, H. I.; Parkin, D. P.
    Objective. Development of easy, practical methods for the management and optimisation of therapeutic diphenylhydantoin (DPH) concentrations in children. Design: Investigation of DPH concentration profiles and pharmacokinetic parameters in children with poorly controlled epilepsy. Subsequent determination of individual-specific DPH maintenance dosage and volume of distribution data suitable for use in routine therapeutic concentration management procedures. Setting. Department of Paediatrics and Child Health and Department of Pharmacology, University of Stellenbosch, Tygerberg Hospital. Subjects. Children of both sexes between the ages of 4 and 12 years with poorly controlled epilepsy receiving DPH as sole medication. Results. In all subjects evaluated epilepsy was unsatisfactorily controlled because of inadequate DPH dosage regimens. Individual-specific maintenance dosage and volume of distribution data could be calculated for all individuals participating in the trial. The calculated data were suitable for use in routine management procedures and in no instance was it necessary to recalculate parameters in a 12-month follow-up period subsequent to evaluation. Conclusions. Therapeutic DPH concentration profiles can be managed satisfactorily in children if individual-specific DPH pharmacokinetic parameters are derived and skilfully applied.