Iwan Darmansjah

Dapsone N‐acetylation, metoprolol α‐hydroxylation, and S‐mephenytoin 4‐hydroxylation polymorphisms in an Indonesian population: A cocktail and extended phenotyping assessment trial

We examined dapsone N‐acetylation and metoprolol α‐hydroxylation and S‐mephenytoin 4‐hydroxylation phenotypings using the respective test probes (dapsone and racemic metoprolol and mephenytoin) administered separately and in a cocktail manner to an Indonesian subject group (n = 30). After ascertaining that the separate and cocktail phenotyping tests of the probe drugs correlated with each other (all rs values >0.84; p < 0.001), the cocktail phenotyping assessment was extended to the other 74 Indonesians. In a total of 104 Indonesians phenotyped with the cocktail test, a visual antimode was apparent only in the dapsone N‐acetylation and S‐mephenytoin 4‐hydroxylation polymorphisms: the frequencies of slow acetylators and poor hydroxylators were 43.3% (95% confidence interval, 33.7% to 52.8%) and 15.4% (95% confidence interval, 8.5% to 22.3%), respectively. The distribution histogram and pro‐bit plots of the metabolic ratio of metoprolol gave no clear evidence for bimodality, and therefore no poor α‐hydroxylator of metoprolol was considered to exist in the present sample size. The findings indicate that the Indonesian subjects have a greater incidence of slow acetylator phenotype compared with Japanese and Chinese, as well as a frequency of poor metabolizer phenotype of S‐mephenytoin similar to that of Korean and Chinese subjects. They resemble an African population (Nigerians) in metoprolol α‐hydroxylation polymorphism, with no apparent antimode derived from white populations.

Dose‐response variation among different populations

Clinical Pharmacology and Therapeutics (1992) 52, 449–452; doi:10.1038/clpt.1992.170

Pharmacokinetic and Pharmacodynamic Properties of Controlled Release (CR/ZOK) Metoprolol in Healthy Oriental Subjects: A Comparison with Conventional Formulations of Metoprolol and Atenolol

The steady state pharmacokinetics and pharmacodynamics of metoprolol controlled release tablets 100 mg CR/ZOK, was compared with those of metoprolol conventional tablets 100 mg (CT) and atenolol 50 mg (ATL) in ten healthy Oriental men. The study was of double‐blind, cross‐over placebo controlled design. The three study drugs and placebo were given in a random order once daily for 4 consecutive days with 1‐week wash‐out between each period. Treadmill exercise tests were performed and blood samples were obtained at fixed intervals after the fourth dose of each treatment.

The Indonesian Drug Advisory Committee and the drug approval process.

The Indonesian Food and Drug Agency began to evaluate drug applications in the early 1970s through an Advisory Committee. This was in response to the perestroika-like policy applied to our drug industry; nowadays there are more than 300 drug companies formulating some 13,5600 drug products. During 1977-1988, 603 drugs were evaluated by the Advisory Committee; 66% were single drugs and 34% were fixed dose combinations. Nine-hundred and twenty-five sessions were needed to arrive at decisions. Most of the applications (88.5%) were reviewed in one or two sessions but 8 drugs took 6-12 sessions. The time needed for assessment may vary from 1 to 3 months (61%), but some have needed almost a year and a half. There were 60% acceptances for single drugs and 35% for fixed combinations.

An Asian Perspective on Drug and Related Health Care Information

To ensure that drugs are available in adequate quantity and quality for the health needs of the population and properly used, Asian governments in the past decades have exercised their sovereign rights quite independently and differently. A high number of patients per prescribing physician has consequences for drug information, in regard to both prescribers and consumers needing to self-medicate. To reliably inform patients through physicians, pharmacists, or medical auxiliary personnel is of great importance in the face of an illiteracy problem. Self-medication and illiteracy place emphasis on communication by word of mouth or by pictures. Word of mouth is the most important route, because even with a steady increase in literacy, the increase in transistor radios has been even more pronounced. For specific health information, instructional posters, with emphasis on pictures, have been very effective. Billboards do not allow adequate information disclosure needed for drugs. The opportunity to expand the coverage of consumer drug information, in that labeling for consumers gives additional relevant general health information, seems appropriate.

The Current Status of Clinical Trials in Indonesia

Clinical trials in developing countries are under attack by several critics, who claim that the poor quality does not justify publication of results and repetition of trials is considered wasteful. There is truth in these arguments when one considers the bad studies sponsored by either local or multinational companies aimed merely at promotion. In the past, clinical trials in Indonesia were primarily marketing studies, but during the last decade a trend of improvement has been seen where early-phase studies are being performed. International standards are being pursued slowly with the introduction of International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. Clinical trials for registration approvals are not required in Indonesia, except when the need becomes obvious at premarketing evaluation. While Indonesia must work hard to train investigators, monitors, and clinical coordinators, the government should lay a legal basis for clinical trials. Contract research organizations could be the driving force in establishing clinical trials in Indonesia which meet international quality standards.