Pharmacokinetics and dosing rationale of Para-Aminosalicylic acid in children and the evaluation of the in vitro metabolism of Ethionamide, Terizidone and Para-aminosalicylic acid (Record no. 19709)
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| 000 -LEADER | |
|---|---|
| fixed length control field | 03932nam a22002177a 4500 |
| 003 - CONTROL NUMBER IDENTIFIER | |
| control field | OSt |
| 005 - DATE AND TIME OF LATEST TRANSACTION | |
| control field | 20240305193737.0 |
| 008 - FIXED-LENGTH DATA ELEMENTS--GENERAL INFORMATION | |
| fixed length control field | 221125b |||||||| |||| 00| 0 eng d |
| 028 ## - PUBLISHER OR DISTRIBUTOR NUMBER | |
| Source | Phone: +255 28 298 3384 |
| Source | Fax: +255 28 298 3386 |
| Source | Email: vc@bugando.ac.tz |
| Source | Website: www.bugando.ac.tz |
| 040 ## - CATALOGING SOURCE | |
| Language of cataloging | English |
| Transcribing agency | DLC |
| 041 ## - LANGUAGE CODE | |
| Language code of text/sound track or separate title | English |
| 100 ## - MAIN ENTRY--PERSONAL NAME | |
| Personal name | Anthony Cuthbert Liwa |
| 9 (RLIN) | 46000 |
| 245 ## - TITLE STATEMENT | |
| Title | Pharmacokinetics and dosing rationale of Para-Aminosalicylic acid in children and the evaluation of the in vitro metabolism of Ethionamide, Terizidone and Para-aminosalicylic acid |
| 260 ## - PUBLICATION, DISTRIBUTION, ETC. | |
| Place of publication, distribution, etc. | Mwanza, Tanzania: |
| Name of publisher, distributor, etc. | Institution Stellenbosch: Stellenbosch University & |
| -- | Catholic University of Health and Allied Sciences [CUHAS – Bugando] |
| Date of publication, distribution, etc. | 2012 |
| 520 ## - SUMMARY, ETC. | |
| Summary, etc. | ABSTRACT: <br/><br/>BACKGROUND: The emergence of mycobacterium tuberculosis resistance to first line drugs has renewed interest in second-line anti-tuberculosis drugs. Generally, Paraaminosalicylic acid (PAS) is less potent and frequently more toxic than the first line drugs. Furthermore, the pharmacokinetics of PAS in children has not been well characterized. <br/><br/>AIMS: The aims of the present study were (1) to determine the pharmacokinetics of PAS in pediatric patients, (2) to describe the discrepancy between children and adult pharmacokinetics and the appropriate dosing regimen of PAS and (3) to investigate the potential of the second-line anti-tuberculosis drugs PAS, terizidone and ethionamide (often used as first-line drug in children) to inhibit the catalytic activities of CYP450 1A2 and 2C9. <br/><br/>PATIENTS: Twenty two patients with drug resistant tuberculosis were included in the study. Ten patients were children with mean age of 4.2 years (range: 1 to 12 years). Twelve patients were adults with mean age of 31.3 years (range: 18 to 53). 4 children (40%) and 4 adults (33.3%) were HIV positive and were on ART. <br/><br/>METHODS: Children received 75 mg/kg twice daily on the first visit and after two weeks they received 150 mg/kg once. Adults received a standard 4 g twice daily. Blood samples were taken at different time points after the dose. In the additional study, the inhibitory effects of PAS, ethionamide and terizidone on phenacetin O-deethylation, a marker substrate of CYP1A2 and diclofenac 4’-hydroxylation, a marker substrate of CYP2C9, were studied using human liver microsomes. <br/><br/>RESULTS: For the 75 mg/kg dose, the mean AUC was 233.3 =g•h/ml and the mean CL was 10.4 l/h/kg. The mean of the observed Cmax of the drug was 45.4 =g/ml and the mean Tmax was 4.8 hrs. For the 150 mg/kg dose, the mean AUC of PAS was 277.9 =g•h/ml and the mean CL was 47.1 l/h/kg. The mean of the observed Cmax of the drug was 56.5 =g/ml and the mean Tmax was 4.8 hrs. On the first visit the mean AUC was 368 =g•h/ml and the mean CL was 13.2 l/h/kg. The mean of the observed Cmax of PAS was 51.3 =g/ml and the mean Tmax was 5.2 hrs. On the second visit the mean AUC was 230 =g•h/ml and the mean CL was 23.9 l/h/kg. The mean of the observed Cmax of PAS was 37.6 =g/ml and the mean Tmax was 5.2 hrs. The comparisons between pharmacokinetics profile of PAS and patients characteristics e.g. age, indicated no statistically significant differences between children (both treatment regimens) and adult patients as well as HIV positive and negative patients. In the in vitro study, all drugs demonstrated no inhibition potency towards the investigated CYP450 enzymes. <br/><br/>CONCLUSIONS:The dose of 75 mg/kg twice daily in children appears to be appropriate to achieve serum concentration above the PAS minimum inhibitory concentration of approximately 1 =g/ml. PAS, ethionamide and terizidone are unlikely to affect the metabolism of concomitantly administered medications that are metabolized by either CYP450 1A2 and/or 2C9 isoenzymes. |
| 856 ## - ELECTRONIC LOCATION AND ACCESS | |
| Uniform Resource Identifier | <a href="http://scholar.sun.ac.za/handle/10019.1/20165">http://scholar.sun.ac.za/handle/10019.1/20165</a> |
| 942 ## - ADDED ENTRY ELEMENTS (KOHA) | |
| Source of classification or shelving scheme | ddc |
| Koha item type | RESEARCH ARTICLES |
| Withdrawn status | Lost status | Source of classification or shelving scheme | Damaged status | Not for loan | Collection | Home library | Current library | Shelving location | Date acquired | Total checkouts | Barcode | Date last seen | Copy number | Price effective from | Koha item type |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MWALIMU NYERERE LEARNING RESOURCES CENTRE-CUHAS BUGANDO | MWALIMU NYERERE LEARNING RESOURCES CENTRE-CUHAS BUGANDO | 11/25/2022 | RA0917 | 11/25/2022 | RA0917 | 11/25/2022 | RESEARCH ARTICLES |