Practical management of therapeutic diphenylhydantoin concentrations in children

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

Oligomeric substances in ampicillin preparations : a comparison of Penbritin, Famicillin and Petercillin

CITATION: Van der Bijl, P. et al. 1988. Oligomeric substances in ampicillin preparations : a comparison of Penbritin, Famicillin and Petercillin. South African Medical Journal, 73:453-455.The original publication is available at http://www.samj.org.zaAn 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.Publisher’s versio

The pharmacokinetics of enteral antituberculosis drugs in patients requiring intensive care

The original publication is available at http://www.samj.org.zaBackground. 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.Publishers' Versio

The pharmacokinetics of enteral antituberculosis drugs in patients requiring intensive care

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 high-performance 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

TNFA-863 polymorphism is associated with a reduced risk of Chronic Obstructive Pulmonary Disease: A replication study

<p/> <p>Background</p> <p>TNF-α mediated inflammation is thought to play a key role in the respiratory and systemic features of Chronic Obstructive Pulmonary Disease. The aim of the present study was to replicate and extend recent findings in Taiwanese and Caucasian populations of associations between COPD susceptibility and variants of the <it>TNFA </it>gene in a Spanish cohort.</p> <p>Methods</p> <p>The 3 reported SNPs were complemented with nine tag single nucleotide polymorphisms (SNP) of the <it>TNFA </it>and <it>LTA </it>genes and genotyped in 724 individuals (202 COPD patients, 90 smokers without COPD and 432 healthy controls). Pulmonary function parameters and serum inflammatory markers were also measured in COPD patients.</p> <p>Results</p> <p>The <it>TNFA </it>rs1800630 (-863C/A) SNP was associated with a lower COPD susceptibility (ORadj = 0.50, 95% CI = 0.33-0.77, p = 0.001). The -863A allele was also associated with less severe forms of the disease (GOLD stages I and II) (ORadj = 0.303, 95%CI = 0.14-0.65, p = 0.014) and with lower scores of the BODE index (< 2) (ORadj = 0.40, 95%CI = 0.17-0.94, p = 0.037). Moreover, the -863A carrier genotype was associated with a better FEV₁percent predicted (p = 0.004) and a lower BODE index (p = 0.003) over a 2 yrs follow-up period. None of the <it>TNFA </it>or <it>LTA </it>gene variants correlated with the serum inflammatory markers in COPD patients (p > 0.05).</p> <p>Conclusions</p> <p>We replicated the previously reported association between the <it>TNFA </it>-863 SNP and COPD. <it>TNFA </it>-863A allele may confer a protective effect to the susceptibility to the disease in the Spanish population.</p

Permeability of intestinal mucosa to crystalline and tabletted isoniazid (INH)

CITATION: Van der Bijl, P., Seifart, H. I. & Van Eyk, A. D. 2003. Permeability of intestinal mucosa to crystalline and tabletted isoniazid (INH). South African Medical Journal, 93(2):127-128.The original publication is available at http://www.samj.org.zaWhen 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.Publisher’s versio

Practical management of therapeutic diphenylhydantoin concentrations in children

CITATION: Smit, A. et al. 1999. Practical management of therapeutic diphenylhydantoin concentrations in children. South African Medical Journal, 89(10):1092-1097.The original publication is available at http://www.samj.org.zaObjective. 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.Publisher’s versio