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. There was less fluctuation in the plasma level-time profile after CR/ZOK than CT and ATL. Plasma concentrations were significantly higher on CR/ZOK than CT at 24 hours after dosing. The relative bioavailability of CR/ZOK to CT was 69.0%. CR/ZOK achieved relatively more uniform beta-blocking effect over the dose interval. Compared to CT and ATL, the peak effect after CR/ZOK was less pronounced and the beta-blockade after 24 hours more effective.
We examined dapsone N-acetylation and metoprolol alpha-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 probit plots of the metabolic ratio of metoprolol gave no clear evidence for bimodality, and therefore no poor alpha-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 alpha-hydroxylation polymorphism, with no apparent antimode derived from white populations.
1 The metabolism of proguanil (PG) was studied by measuring PG, cycloguanil (CG) and 4-chlorophenylbiguanide (CPB) in plasma and urine samples after an oral 200 mg dose of PG hydrochloride administered to 14 extensive (EMs) and 10 poor hydroxylators (PMs) of S-mephenytoin of Indonesian origin.2 The mean (± s.d.) values of the elimination half-life (ti/2) and AUC of PG were significantly (P < 0.01) greater in the PM than in the EM group (20.6 ± 3.1 vs 14.6 ± 3.5 (95% confidence intervals of difference 3.1 to 8.9) h; and 5.43 ± 1.89 vs 3.68 ± 0.83 (0.58 to 2.91) gg ml-1 h).3 Plasma concentrations of CG, an active metabolite, could not be detected in all PMs, and those of CPB were sufficiently high to determine a time-course in only four PMs. Mean AUC(0,24 h) values of CPB were significantly (P < 0.05) lower in the PM (n = 4) than in the EM group (n = 14) (0.47 ± 0.13 vs 0.88 ± 0.50 (-0.14 to 0.96) ,ug ml-1 h). (rs = -0.831) metabolic ratios.6 The bioactivation of PG to CG cosegregates with the genetically determined 4'-hydroxylation polymorphism of S-mephenytoin in Indonesian subjects, and the formation of CPB appears to be associated partially with S-mephenytoin 4'-hydroxylation.
We have compared the frequency with which various drugs were used in patients with cerebrovascular disease in five countries (UK, Italy, Indonesia, Spain and Yugoslavia). There were very large variations in the use of anti-oedema agents, ‘cerebral vasodilators’, and vitamins, which were not explained by differences in the populations studied. This variation has probably less to do with any scientific validation for the various treatments, which in most cases does not exist, than with medical ‘fashion’ and commercial pressures. Large variations in prescribing habits for what is thought to be the same disease are undesirable, and reflect a dearth of facts and adequate clinical trials.
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 labelling for consumers gives additional relevant general health information, seems appropriate.
Tujuan pedoman penggunaan antibiotik adalah untuk membinbing penggunaannya secara rasional, sehingga antibiotik digunakan secara efektifdan efisien dengan efek satnping sekecil-kecilnya bagi penderita dan nasyarakat. Tindakan inijuga berdatnpak mengurangi biaya tanpa mengorbankan penderita,hnasyarakat terhadap penilihan antibiotikyang salah. Pedotnan ini harus mernenuhi persyaratan tertentu agar dapat diterima oleh pemakainya dan berlaku bagi sebagian besar (kira-kira 9O%) kclotnpok penderita. Antibiotik terpilih yang diusulkan harus efektif tanpa adanya hasil antibiogratn. Pedoman ini harus berdasarkan pengetahuan mikrobiologi, fannakologi dan klinik. Paratneter farnakologi yang akan dibahas antara lain adalah fannakodinatnik, fannakokinetik, efekbksik dan efek samping, hasil uji klinik, percobaan epidemiologi obat sertafarnakolctgi perbandingan antibiotik. Strategi petnilihan teruta,na berdasarkan penerapan rasio nanfaat-risiko serta biaya; nanfaat antibiotik yang diperkirakan untuk indikasi tertentu harus lebih besar dari kemungkinan risiko yang dapat ditimbulkannya. Prinsip "Priuutn non nocere" haruslah merupakan pertùnbangan utana. Antibiotik sering menimbulkan efek satnping dan karena penberiannya perlu bertujuan jelas. Menganggap bahwa "bila tidak berefek tentunya tidak berbahaya" tidaklah benar. Pedontan bukanlah suutu aturan yang kaku; pertimbangan iltniah harus selalu merupakan petunjuk akhir, terutatna pada keadaan klinik yang konpleks. Pedonan pemilihan antibiotik perlu diperbaharui terus ,nenerus bilatnana ada infonnasi yang baru. LaTitnnya tidak perlu ada sanksi terhadap penyinpangan kecil dari pedotnan yang ada, namun penyitnpangan jauh dari suatu pedoman menerlukan dasar ilniah yang jelas.
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