Government Pharmaceutical Organization Research Articles

A randomized, open-label, 2-period, crossover bioequivalence study of two oral formulations of 75 mg oseltamivir in healthy Thai volunteers

Oseltamivir, an ester prodrug of its active carboxylate metabolite, is an effective neuraminidase inhibitor used to treat influenza A and B virus infections. The purpose of this study was to compare the bioavailability of two 75 mg oral formulations of oseltamivir: a generic drug, GOP-A-Flu (test, Government Pharmaceutical Organization, Thailand) and Tamiflu (reference, Hoffmann-La Roche Ltd., Nutley, NJ, USA) in healthy volunteers. A single-dose, randomized, 2-sequence, crossover study was conducted in 24 healthy Thai volunteers. Each volunteer received a 75 mg capsule of the reference or test drugs under fasting conditions. Blood samples were collected before dosing and at various time points up to 48 hours after dosing and analyzed for plasma oseltamivir and oseltamivir carboxylate concentrations. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-infinity, tmax and t1/2 were analyzed using the non-compartmental method. Drug safety was assessed. 23 volunteers completed both treatment periods. The geometric mean ratios (test/reference) between the two formulations of oseltamivir were 96.83% (90% CI, 76.85 - 123.15%) for Cmax 103.66% (86.44 - 113.56%) for AUC0-t, and 103.98% (86.44 - 113.56%) for AUC0-infinity. Those of oseltamivir carboxylate were 102.17% (90% CI, 90.90 - 109.10%) for Cmax, 103.95% (90.90 - 109.10%) for AUC0-t, and 103.95% (90.92 - 109.08%) for AUC0-infinity. No significant difference of the tmax of oseltamivir and oseltamivir carboxylate between the two formulations was detected (p > 0.05). Both formulations were well-tolerated. Although the Cmax of oseltamivir was the only parameter not entirely within the equivalence criteria, the two capsule formulations were considered bioequivalent in terms of rate and extent of absorption regarding its active carboxylate metabolite.

Evaluation of the safety and relative bioavailability of a new dihydroartemisinin tablet formulation in healthy Thai volunteers

A new dihydroartemisinin (DHA) tablet formulation has been developed by the Thai Government Pharmaceutical Organization (GPO). In this report, its in vitro dissolution and in vivo pharmacokinetics as well as its safety in healthy volunteers were evaluated, using the DHA tablet made by Dafra Pharma NV as a reference. A two-period crossover clinical study design was utilised. Twenty-four volunteers were randomly allocated to two sequences (12 volunteers in each) to receive a 200mg single oral dose of either the GPO or Dafra formulation with a wash-out period of 5-7 days. In vitro, the GPO formulation dissolved more readily. In vivo, the GPO formulation had a higher maximum plasma concentration and approximately 149% (90% CI 125-179%) greater bioavailability. Both formulations were well tolerated. Interestingly, significant decreases in haemoglobin and haematocrit values (P<0.001) were noted following administration of one dose of DHA (decrease of 0.73 g/dl haemoglobin and 2.0% haematocrit compared with baseline) or two doses of DHA (decrease of 0.95 g/dl haemoglobin and 3.3% haematocrit compared with baseline). The second dose was associated with additional toxicity compared with one dose with regard to haematocrit (P<0.001) but not haemoglobin. This finding warrants further investigation, since the drug will be used for the treatment of malaria in which anaemia is a consequence.

Productivity/performance measurement

PurposeTo address two key problems facing the production department at the government pharmaceutical organization (GPO). They were a lack of productivity and performance measurement at the operational level, and a need to assess the functional readiness to undertake its own performance‐analysis work.Design/methodology/approachThe decision was made to apply the multi‐factor productivity measurement model (MFPMM). This was due to its ability to link with existing data that had been generated by the accounting department, its explicit integration between productivity and financial performance (i.e. profitability) at the operational level, and its major features such as information on opportunity gain/loss.FindingsFor the GPO, it was quite clear that productivity improvement would represent the critical direction for the production department in the future. Based on its initial deployment at the Section 3 unit, the MFPMM was generally viewed as a suitable tool for measuring and providing necessary productivity/performance information.Practical implicationsThe database management needed to be improved in order to ensure timely provision of data into the MFPMM. Furthermore, better performance‐analysis capability by the staffs was required. In other words, both technical and managerial aspects must be recognized in order to ensure the MFPMM success and sustainability.Originality/valueThis study generated insightful information into operational performance at the GPO. It was clear that productivity represented the basis for formulating future policy initiatives.

Neurological complications in AIDS patients receiving HAART: a 2‐year retrospective study

The positive role of highly active anti-retroviral therapy (HAART) in reducing opportunistic infections in acquired immunodeficiency syndrome (AIDS) patients is well known. However, case reports from around the world have demonstrated that some patients seem to suffer a paradoxical deterioration of health as their immune function improves with treatment. This phenomenon has been called immune restoration inflammatory syndrome (IRIS). In northern Thailand, GPO-vir (Stavudine-D4T + Lamivudine-3TC + Nevirapine-NVP) has been promoted for the treatment of AIDS patients since April 2002, in accordance with the Government Pharmaceutical Organization's guidelines. However, the incidence rates of IRIS affecting nervous system (NIRIS) and non-NIRIS in comparison with the previous incidence of AIDS-defining disease have not been reported. We conducted a retrospective study to review the incidence of NIRIS and non-NIRIS in AIDS patients treated with GPO-vir in Chiang Mai University Hospital, Thailand, between May 2002 and April 2004. We compare these incidence rates with the incidence rates of neurological complications in the pre-HAART era. Altogether 506 AIDS patients were treated with GPO-vir during the specified period. The overall incidence of NIRIS, including progressive multifocal leukoencephalopathy (PML), cerebral toxoplasmosis and cytomegalovirus (CMV) retinitis, was lower than the previous incidence of AIDS-defining disease in the pre-HAART era. However, the incidence of ischemic stroke, hemorrhagic stroke and primary central nervous system (CNS) lymphoma had increased.

Antiretroviral medications--from Thailand to Africa.

The international AIDS conference highlighted the substantial progress that Thailand has made in reducing the frequency of mother-to-child transmission of HIV and providing antiretroviral treatment. Now, Krisana Kraisintu, the Thai pharmaceutical chemist who helped to spearhead her nation's response to AIDS, has embarked on a self-assigned mission — to bring affordable antiretroviral treatment to three African countries.Kraisintu is the former director of the Research and Development Institute of the Government Pharmaceutical Organization (GPO) in Thailand and a pioneer in the production of generic antiretroviral medications. In 1995, she brought antiretroviral treatment to Thailand by producing zidovudine to protect newborns . . .

Thailand's Do-It-Yourself Therapy

NEWS FOCUS SPECIAL REPORTBANGKOK, THAILAND-- In April 2002, the Government Pharmaceutical Organization (GPO) here began producing a generic version of three anti-HIV drugs--d4T, 3TC, and nevirapine--mixed together into one pill called GPO-VIR. Treatment requires only two pills a day, each of which costs a mere 50 cents. This story is part of a series on HIV/AIDS in Asia; the stories in this initial installment focus on Myanmar, Vietnam, Cambodia, and Thailand.

A comparison of three different dihydroartemisinin formulations for the treatment of acute uncomplicated falciparum malaria in Thailand

We compared the safety and efficacy of three formulations of dihydroartemisinin for the treatment of acute uncom- plicated falciparum malaria in patients who received a total dose of 600 mg dihydroartemisinin over 5 days. The first group was treated by dihydroartemisinin produced and formulated in the People’s Republic of China, the second group was treated by dihydroartemisinin produced in Vietnam but formulated by the Government Pharmaceutical Organization of Thailand and the third group was treated by dihydroartemisinin produced and formulated by the Government Pharmaceutical Organization of Thailand. All patients were admitted to hospital to evaluate safety and e.cacy for a total of 28 days. By the third day of treatment, most patients were blood-smear negative for parasites and none had serious adverse effects. Minor symptoms such as nausea, dizziness and headache were similar in the three groups and disappeared after 3 days of treatment. One-hundred and thirty-three patients completed the 28-day follow- up period. The cure rates of groups I, II and III were 80%, 85% and 92%, respectively (P 0.02). There were no significant differences in fever clearance or parasite clearance among the three groups. We conclude that the three formulations of dihydroartemisinin produced and formulated in different countries were safe and effective in treating uncomplicated falciparum malaria acquired in Thailand. © 1998 Australian Society for Parasitology. Published by Elsevier Science Ltd.

Pharmacokinetics of Three Commercial Antivenoms in Patients Envenomed by the Malayan Pit Viper, Calloselasma Rhodostoma, in Thailand

The pharmacokinetics of 3 monospecific antivenoms were compared in patients envenomed by the Malayan pit viper, Calloselasma rhodostoma. There was a biphasic decline in serum concentrations following intravenous administration. The initial rapid decline was attributable to the formation of venom-antivenom complexes, as the fall in antivenom during this phase was positively correlated with the initial venom concentration (P = 0.045). The total apparent volume of distribution for each antivenom was 1.5-3 times larger than that of the central compartment, which suggests some tissue distribution in addition to complex formation. This was marked for antivenom from the Government Pharmaceutical Organization of Thailand which contained mostly F(ab)2 fragments. The terminal elimination half time was shorter for Twyford antivenom of caprine origin. Systemic clearance was lower for Thai Red Cross antivenom. In 8 of the 26 patients who experienced recurrence of non-clotting blood after initial response to antivenom, serial measurements of plasma venom and antivenom concentrations revealed that recurrence of venom antigenemia and non-clotting blood bore no direct relation to the elimination half-life of the antivenom used, but non-clotting blood recurred when serum antivenom levels fell below 10-20% of the total given. There is no substitute for close monitoring of envenomed patients so that indications for further antivenom can be detected promptly.