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Can anybody assist and advise me on this topic.
I would like to do a PK studies for anti-TB drugs (rifampicin,
isoniazid, pyrazinamide, and ethambutol) for both children and
adults. PK of these drugs in my country is unknown. HIV infection is
thought to contribute to high TB death rate. The NTP is uncertain
whether in the context of high tb hiv burden and the well established
community DOT system, these (TB) patients attain optimal plasma drug
levels.
I would like to determine rich data for rifampicin, isoniazid,
pyrazinamide and ethambutol in a small group of adult patients and
similar profiles will be determined on rifampicin and isoniazid in
children. These rich data will be used to create a PK model for each
drug. A population PK study will then be followed where a single
sample will be collected from other patients in the intensive phase
of their treatment and attempt to identify factors that influences
drug PK Studies.
Target population for the study are the few patients that are
inpatients (hospitalised) and the patients attending an out patient
TB clinic (probably 100 each group as discussed) within the facility
that will be involved in the study.
Questions:
1. What do you think are the limitation factors to this study?
2. Other than looking at the PK profile and the co-variants which
affect the PK of TB drugs taken during the intensive phase of
treatment, what else might be of importance to look for while
conducting the study?
Any points of clarification is welcomed.
My regards,
Andrew.
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The following message was posted to: PharmPK
My first question would be why you want to conduct PK study, since the
drugs mentioned are already established and reported data are
available. If
you want to conduct BE study then population has to be adequate to
minimize the variability among the subject and statistical calculations.
Dr. Subhash Pande
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The following message was posted to: PharmPK
Dear Andrew,
The PK of isoniazid is highly variable due to 2 underlying
subpopulations, fast and slow acetylators.
Therefore, you need sufficient full PK data to characterize these
subgroups.
Of note, there is already a lot of PK data available in the
literature, both in children and adults, even a population PK model
on isoniazid, rifampin, and pyrazinamide is available (Population
pharmacokinetic modeling of isoniazid, rifampin, and pyrazinamide.
Peloquin CA, Jaresko GS, Yong CL, Keung AC, Bulpitt AE, Jelliffe RW.
Antimicrob Agents Chemother. 1997 Dec;41(12):2670-9).
I suggest you use literature data to build your base population PK
model and only apply sparse PK sampling to determine the specific PK
in your country.
Best regards,
Kees
Kees Bol, Ph.D. > Project Manager/Senior Consultant
--
Kinesis Pharma BV > Consultants in Drug Development
Lage Mosten 29, 4822 NK BREDA, The Netherlands
www.kinesis-pharma.com
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Why do I want to conduct such a study? Yes I know studies on the same
have been conducted but what I am interested in is whether the
optimal serum levels of these drugs in the my TB patients in my
country, whether smear positive or smear negative and HIV positive or
HIV negative, is achieved.
Regards,
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The following message was posted to: PharmPK
Hi -
We have done studies in several locations regarding TB drug absorption,
including North America, Africa, and South America. At this point, most
agree that malabsorption does occur, and the larger question is the
effect
on outcome. The top 2 references below clearly show there is an
effect, and
the others provide additional detail.
We can discuss further.
Weiner M, Benator D, Burman W, Peloquin CA, Khan A, Vernon A, Jones B S,
Silva-Trigo C, Zhao Z, Hodge T and the Tuberculosis Trials Consortium.
Association Between Acquired Rifamycin Resistance and the
Pharmacokinetics
of Rifabutin and Isoniazid among Patients with HIV and Tuberculosis.
Clinical Infectious Diseases 2005; 40: 1481-1491.
Tappero JW, Bradford WZ, Agerton TB, Hopewell P, Reingold A, Lockman S,
Oyeri R, Talbot E, Kenyon T, Moetti T, Moffat H, Peloquin CA. Serum
Concentrations of Antimycobacterial Drugs in Patients with Pulmonary
Tuberculosis in Botswana. Clinical Infectious Diseases 2005; 41:
461-469.
Weiner M, Bock N, Peloquin CA, Burman WJ, Khan A, Vernon A, Zhao Z,
Weis S,
Sterling T, Hayden K, Goldberg S and the Tuberculosis Trials Consortium.
Pharmacokinetics of Rifapentine 600, 900 and 1,200 mg during Once-Weekly
Tuberculosis Therapy. American Journal of Respiratory and Critical Care
Medicine. American Journal of Respiratory and Critical Care Medicine
2004;
169: 1191-1197.
Peloquin C. Use of Therapeutic Drug Monitoring in Tuberculosis Patients
(editorial) Chest 2004; 126: 1722-1724.
Peloquin CA. Therapeutic Drug Monitoring in the Treatment of
Tuberculosis.
Drugs 2002; 62: 2169-2183
Thanks,
Chuck
Charles Peloquin, Pharm.D.
Director, Infectious Disease
Pharmacokinetics Laboratory, Rm. K-424a
National Jewish Medical and Research Center
1400 Jackson St.
Denver, CO 80206
tel: (303) 398-1427
fax: (303) 270-2229
e-mail: peloquinc.aaa.njc.org
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