MyMedR

Pharmacokinetics of artemisinin-type compounds

Navaratnam V, Mansor SM, Sit NW, Grace J, Li Q, Olliaro P

Clin Pharmacokinet, 2000 Oct;39(4):255-70.

Various compounds of the artemisinin family are currently used for the treatment of patients with malaria worldwide. They are characterised by a short half-life and feature the most rapidly acting antimalarial drugs to date. They are increasingly being used, often in combination with other drugs, although our knowledge of their main pharmacological features (including their absorption, distribution, metabolism and excretion) is still incomplete. Such data are particularly important in the case of combinations. Artemisinin derivatives are converted primarily, but to different extents, to the bioactive metabolite artenimol after either parenteral or gastrointestinal administration. The rate of conversion is lowest for artelinic acid (designed to protect the molecule against metabolism) and highest for the water-soluble artesunate. The absolute and relative bioavailability of these compounds has been established in animals, but not in humans, with the exception of artesunate. Oral bioavailability in animals ranges, approximately, between 19 and 35%. A first-pass effect is highly probably for all compounds when administered orally. Artemisinin compounds bind selectively to malaria-infected erythrocytes to yet unidentified targets. They also bind modestly to human plasma proteins, ranging from 43% for artenimol to 81.5% for artelinic acid. Their mode of action is still not completely understood, although different theories have been proposed. The lipid-soluble artemether and artemotil are released slowly when administered intramuscularly because of the 'depot' effect related to the oil formulation. Understanding the pharmacokinetic profile of these 2 drugs helps us to explain the characteristics of the toxicity and neurotoxicity. The water-soluble artesunate is rapidly converted to artenimol at rates that vary with the route of administration, but the processes need to be characterised further, including the relative contribution of pH and enzymes in tissues, blood and liver. This paper intends to summarise contemporary knowledge of the pharmacokinetics of this class of compounds and highlight areas that need further research.

Matched MeSH terms: Malaria/drug therapy

Estimated coefficient of variation values for sample size planning in bioequivalence studies

Yuen KH, Wong JW, Yap SP, Billa N

Int J Clin Pharmacol Ther, 2001 Jan;39(1):37-40.

PMID: 11204936

OBJECTIVE: The aim of the present communication is to provide information regarding the intrasubject coefficent of variation obtained from 30 bioequivalence studies covering 16 drugs which can be used for estimation of sample size. Additionally, an attempt was also made to estimate the test power of each of the studies conducted.

METHODS: The intrasubject coefficient of variation was estimated from the residual mean square error obtained from analysis of variance of the parameters AUC0-infinity, Cmax and Cmax/AUC0-infinity after logarithmic transformation. The test power in the analyses of the above parameters was subsequently estimated using nomograms provided by Diletti et al. [1991].

RESULTS AND CONCLUSION: Thirty products covering 16 drugs were studied in which 22 were immediate-release (including one dispersible tablet) and 8 were sustained-release formulations. The intrasubject coefficient of variation for the parameter AUC0-infinity was smaller than Cmax, and hence considerably more studies were able to attain a power of greater than 80% using 12 volunteers for the AUC0-infinity, compared to the Cmax. However, the variability in the Cmax could be reduced by using the parameter Cmax/ AUC0-infinity, and thus, provide a more realistic estimation of sample size, since the latter reflects only the rate of absorption and not both the rate and extent as in the case of Cmax [Endrenyi et al. 1991].

Matched MeSH terms: Drug Therapy/statistics & numerical data*

Fulltext Enzyme replacement therapy for Gaucher Disease: the only experience in Malaysia

Chan LL, Lin HP

Med J Malaysia, 2002 Sep;57(3):348-52.

PMID: 12440275 MyJurnal

Gaucher Disease may now be treated with enzyme replacement therapy (ERT) or bone marrow transplantation (BMT). Both have their advantages and disadvantages. Results with BMT are curative when successful but limited by the scarcity of an appropriate donor. ERT offers very good relief of symptoms but treatment is lifelong and cost of treatment exorbitant. Patients in developing countries are particularly disadvantaged and management remains a dilemma for both doctor and patient.

Matched MeSH terms: Gaucher Disease/drug therapy*

Fulltext Penicillium marneffei infection in a non aids patient: first case report from Malaysia

Saadiah S, Jeffrey AH, Mohamed AL

Med J Malaysia, 1999 Jun;54(2):264-6.

PMID: 10972040

Penicillium marneffei, a dimorphic fungus is a rare opportunistic pathogen. It is known to cause infection in immunocompromised patients and recently its occurrence in AIDS patients has been well-documented. Disease with Penicillium marneffei is even rarer among previously healthy individuals. The disease is endemic in Southeast Asia and China. Recognition of this rare disease is important because it is amenable to treatment. We report a case of P. marneffei infection in a previously healthy individual.

Matched MeSH terms: Mycoses/drug therapy

Fulltext Typhoid fever: present and future

Merican I

Med J Malaysia, 1997 Sep;52(3):299-308; quiz 309.

PMID: 10968104

Typhoid fever (TF), a systemic prolonged febrile illness, continues to be a worldwide health problem especially in developing countries where there is poor sanitation and poor standards of personal hygiene. The worldwide incidence of TF is estimated to be approximately 16 million cases annually with 7 million cases occurring annually in SE Asia alone. More than 600,000 people die of the disease annually. The pathogenesis of TF is beginning to be understood. The clinical features and diagnosis of TF are well known. New diagnostic methods have yet to gain universal acceptance. Traditional treatment with the first-line antibiotics (i.e. chloramphenicol, ampicillin and trimethoprim-sulphamethoxazole) though still being used in most developing countries are gradually being replaced with shorter courses of treatment with third generation cephalosporins or fluoroquinolones especially with the growing incidence of multi-drug resistant S typhi strains (MDR-ST). MDR-ST strains are particularly common in the Indian subcontinent; Pakistan and China. The presently available vaccines are far from satisfactory in terms of safety, efficacy and costs. Newer vaccines have been developed and are presently undergoing clinical trials in human volunteers.

Matched MeSH terms: Typhoid Fever/drug therapy*

Delays in thrombolytic therapy in acute myocardial infarction: an audit from the east coast of peninsular Malaysia

Loke YK, Hwang SL, Tan MH

Ann Acad Med Singap, 1997 May;26(3):285-9.

PMID: 9285018

The objectives of this study were to evaluate the time delays between the onset of symptoms and admission to hospital and provision of thrombolytic therapy in patients with suspected acute myocardial infarction; and to examine the accuracy of the clinical diagnosis and the therapeutic decision on thrombolysis in these patients. An observational study of 96 patients with suspected myocardial infarction was undertaken over a period of 15 months in the Coronary Care Unit of Hospital Kuala Terengganu. Seventy per cent of the patients arrived in the hospital within 6 hours of the onset of symptoms. After arrival in the emergency room, it took a median time of 85 minutes before the administration of thrombolytic therapy. Of the 67 patients who were given thrombolysis, 46 were treated within 6 hours of the onset of symptoms. About a quarter of patients said that they had delayed seeking treatment at the hospital. Treatment delays occurring in the hospital were mainly due to admission procedures as well as late diagnosis. Eighty-one patients had confirmed myocardial infarction of whom 59 received thrombolytic therapy. Eight patients receiving thrombolytic therapy had no confirmation of myocardial infarctions. Improvements in diagnostic accuracy and reduction of delays in the provision of thrombolytic therapy could be achieved by better training of health care staff as well as by further streamlining of admission procedures.

Matched MeSH terms: Myocardial Infarction/drug therapy*

Fulltext Helicobacter pylori and peptic ulcer disease--a causal link

Goh KL

Med J Malaysia, 1997 Jun;52(2):161-8.

PMID: 10968075

The link between Helicobacter. pylori and peptic ulcer disease in 1997 is an irrefutable one. The association between infection and ulcerogenesis has been shown to be biologically plausible with induction of epithelial inflammation and cell damage and its effect on gastrin/acid homeostasis. The association of H. pylori infection and peptic ulcer disease is a close and consistent one. There is ample evidence indicating that H. pylori eradication results in virtual abolition of ulcer relapse. Several studies have demonstrated that eradication of H. pylori results in ulcer healing and there is evidence showing a temporal relationship between infection and development of peptic ulcer disease.

Matched MeSH terms: Helicobacter Infections/drug therapy

Fulltext Hookworm infection and reinfection following treatment among Orang Asli children

Norhayati M, Oothuman P, Fatmah MS, Muzain Minudin Y, Zainuddin B

Med J Malaysia, 1995 Dec;50(4):314-9.

PMID: 8668049

In hookworm endemic areas where sanitation is often wanting, reinfection of treated children is a problem. This study was conducted to enumerate the prevalence and the reinfection rate of hookworm in 193 Orang Asli children following treatment with stat dose of 400mg of albendazole at 2 and 4 months post-treatment. All samples were examined using the Kato-Katz and Harada Mori techniques. The overall initial prevalence was 31.0%, with 27.0% in males and 34.0% in females although there was no statistical difference. Only 7.0% of the children had moderate intensity of infection. The overall infection rate at 2 and 4 months post-treatment was 11.0% and 8.0%. New cases were detected at 1.0% and 5.0% at 2 and 4 months post-treatment period. Reinfection rate 2 months post-treatment was 24.0%, and it was 30.0%, 4 months after treatment. All infection at 2 and 4 months post-treatment were light. Long-term strategies incorporating health education on personal hygiene, provision of toilets and safe water supply need to be adopted in these Orang Asli villages to control rapid reinfection.

Matched MeSH terms: Hookworm Infections/drug therapy

Fulltext Dopa responsive dystonia with diurnal fluctuation (Segawa's syndrome)

Ong LC, Tang SF, Lal TR

Med J Malaysia, 1994 Jun;49(2):176-8.

PMID: 8090100

A 10-year-old girl presented with progressive dystonia with diurnal fluctuation. Response to low dose L-Dopa was dramatic and sustained with no complications. Recurrence of symptoms was observed on attempted withdrawal. Because of the dramatic response to therapy, dopa-responsive dystonia must be considered in the differential diagnosis of disorders presenting as gait disorders in childhood.

Matched MeSH terms: Dystonia/drug therapy*

Fulltext Actinomycosis of the accessory breast treated with cotrimoxazole

Mohammed KN

Med J Malaysia, 1993 Jun;48(2):229-31.

PMID: 8350802

Actinomycosis is a chronic suppurative granulomatous disease caused by the filamentous bacteria, Actinomyces israelii, which was once thought to be a fungus. It is a Gram-positive, aerobic or microaerophillic, non acid-fast hyphal organism which fragments into coccoid or bacillary forms and, unlike the fungus, does not form conidia. Accessory breast tissue usually occurs along the milk lines, frequently in the axilla and rarely in the thighs. Actinomycosis of the breast is very uncommon and we report the case of a multiparous woman who had a painful lump in the axilla which, on histopathologic examination, showed actinomycosis within the accessory breast tissue.

Matched MeSH terms: Actinomycosis/drug therapy*

Fulltext All trans-retinoic acid in the treatment of promyelocytic leukaemia--a case report

Hoe TS, Hussin NH, Chum KW, Cheong SK

Med J Malaysia, 1992 Sep;47(3):225-7.

PMID: 1491649

A six year old Chinese boy with relapsed Acute Promyelocytic Leukaemia (APML) failed to respond to reinduction with Daunorubicin and Cytarabine infusion. He was successfully treated with all trans-Retinoic Acid (45 mg/m2/day) orally. After four weeks of treatment, he was in complete remission. The side effects of all trans-Retinoic Acid were negligible.

Matched MeSH terms: Leukemia, Promyelocytic, Acute/drug therapy*

Fulltext Continuous spinal anaesthesia--early experience in University Hospital, Kuala Lumpur

Vijayan R, Chan L, Raveenthiran R

Med J Malaysia, 1995 Dec;50(4):401-10.

PMID: 8668064

Continuous spinal anaesthesia using the incremental technique was used in nineteen high risk patients with multiple medical problems, seventeen of whom were elderly, for lower limb orthopaedic and pelvic surgery. An intrathecal catheter (18G/28G) was inserted under local anaesthesia via the lumbar interspinous space. Spinal anaesthesia was induced with small incremental doses of 0.5% bupivacaine hydrochloride through the intrathecal catheter to achieve the level of analgesia required for surgery. The duration of surgery ranged from 45 to 300 minutes (mean + S.D 100 + 37 min). The initial volume of 0.5% bupivacaine required for surgery ranged from 0.8 ml-2.0 ml (1.2 + 0.7 ml) and the total volume ranged from 0.9 ml to 3.1 ml (mean + S.D 1.4 + 0.7 ml). Haemodynamic stability was well maintained perioperatively. Only two patients required 6 mg of ephedrine and 1 mg of aramine respectively for a greater than 25% reduction in systolic blood pressure with induction of spinal anaesthesia. Intrathecal morphine 0.1-0.3 mg was administered to 15 patients at the end of surgery for postoperative pain relief with good effect. One patient developed late respiratory depression from an inadvertent overdose of intrathecal morphine. No neurological sequelae were noted and no patient developed a postdural puncture headache. The use of the microcatheter was discontinued in the U.S.A and Australia following four case reports of cauda equina syndrome with this technique. Current opinion, however, is that the reported cauda equina syndrome was due to the neurotoxic effects of lignocaine 5% that was used and not due to the microcatheter per se. Continuous spinal anaesthesia is now used widely in Europe when cardiovascular stability is desired in poor risk patients undergoing lower limb and lower abdominal surgery.

Matched MeSH terms: Pain, Postoperative/drug therapy

Fulltext Herpes gestationis: one of the rare skin lesions in pregnancy

Naganathan K, Doi SA, Jamiyah H

Med J Malaysia, 1994 Dec;49(4):401-3.

PMID: 7674975

Herpes gestationis is a rare disease in pregnancy. A 35-year-old G3P2 presented during her third trimester with erythematous pruritic papular eruptions. Direct immunofluorescence of a skin biopsy confirmed the diagnosis of herpes gestationis. The patient responded well to predniosolone treatment.

Matched MeSH terms: Pemphigoid Gestationis/drug therapy

Fulltext Clomid induced combined extrauterine and intrauterine pregnancy--a case report

Ng YT, Wong WP, Puraviappan AP

Med J Malaysia, 1983 Jun;38(2):150-2.

PMID: 6621446

A 23 year old Indian lady, gravida 1 para 0, with Clomid induced pregnancy was admitted to the University Hospital on 29 August 1981 with signs and symptoms of pregnancy and intraperitoneal bleed. Period ofamenorrhoea at time of admission was eight weeks. Emergency laparotomy revealed a right leaking ectopic pregnancy and an enlarged gravid uterus. Ultrasound done on the 7th post operative day confirmed concurrent intrauterine pregnancy which progressed normally to term, ending with a normal healthy baby at 39 weeks through an assisted breech delivery.

Matched MeSH terms: Infertility, Female/drug therapy

Fulltext Penicillin resistant pneumococcus

Jamal F, Tirathram M, Hussin Z

Med J Malaysia, 1983 Jun;38(2):102-3.

PMID: 6621437

The isolation of a penicillm. resistant strain of Streptococcus pneumoniae is being reported and indicates the need to screen pneumococcal isolates for resistance towards antibiotics.

Matched MeSH terms: Pneumococcal Infections/drug therapy

Fulltext Female breast engorgement on ranitidine--a case report

Ray S

Med J Malaysia, 1989 Dec;44(4):351-3.

PMID: 2520048

A 60 year old woman with chronic duodenal ulcer not responding to Cimetidine, was changed to Ranitidine. She had symptomatic improvement, but had bilateral breast engorgement and tenderness for which treatment was discontinued. A therapeutic trial on a second occasion had the same side effect which came on more rapidly and quickly. This complication in such severe form and recurrence on rechallenge requiring withdrawal of drug was observed for the first time with any H2 receptor antagonist.

Matched MeSH terms: Duodenal Ulcer/drug therapy

Fulltext A study of the fasting diabetic patients during the month of Ramadan

Mafauzy M, Mohammed WB, Anum MY, Zulkifli A, Ruhani AH

Med J Malaysia, 1990 Mar;45(1):14-7.

PMID: 2152063

Twenty two Muslim diabetic patients on oral hypoglycaemic agents were studied during the fasting month of Ramadan to determine the effect of fasting on their diabetic control. All the patients completed their fast during the month. Their mean (+/- standard deviation) blood glucose, serum fructosamine and body weight before the fasting month were 10.7 +/- 4.6 mmol/l, 6.64 +/- 3.64 mmol/l and 60.5 +/- 12.6 kg and by the end of the fasting month were 10.9 +/- 4.4 mmol/1,4.34 +/- 1.08 mmol/l and 59.8 +/- 12.3 kg respectively. There was no significant difference between the blood glucose levels but there were significant reductions in the mean body weight and fructosamine values (p = 0.01 and p = 0.03 respectively). The mean decrease in body weight and fructosamine were 0.7 +/- 1.3 kg and 2.29 +/- 3.09 mmol/l respectively. There were also statistically significant differences between the mean daily calorie content before the fasting and during the fasting month (1480 +/- 326 vs 1193 +/- 378 Cal/day - p less than 0.005) and between the mean daily carbohydrate content (389 +/- 298 vs 187 +/- 46 gm/day - p less than 0.005). In conclusion, fasting was safe for diabetic patients on oral hypoglycaemic agents and it was associated with weight reduction and improvement in the overall diabetic control. This was most likely due to decrease in food intake.

Matched MeSH terms: Diabetes Mellitus/drug therapy

Cyclosporine in clinical transplantation and autoimmune disease. The Third Asian Sandimmun Workshop. Penang, Malaysia, November 12-13, 1989. Kaoshing, Taiwan, ROC, November 19-20, 1989. Proceedings

Transplant Proc, 1989 Jun;21(3 Suppl 1):1-113.

PMID: 2741210

Matched MeSH terms: Autoimmune Diseases/drug therapy*

Omeprazole compared with ranitidine once daily in the treatment of duodenal ulcer

Chelvam P, Goh KL, Leong YP, Leela MP, Yin TP, Ahmad H, et al.

J Gastroenterol Hepatol, 1989;4 Suppl 2:53-61.

PMID: 2491362

A double-blind randomized study in 230 Malaysian patients with duodenal ulcer was conducted to compare the proton-pump inhibitor, omeprazole 20 mg, given once daily in the morning, with ranitidine 300 mg, administered once daily at night. After 2 and 4 weeks of treatment, 222 and 220 patients, respectively, were evaluable according to the study protocol. Omeprazole produced significantly higher healing rates than ranitidine at both 2 weeks (75% versus 46%, respectively, P less than 0.0001) and 4 weeks (97% versus 83%, respectively, P = 0.001). Ulcer symptoms were relieved more rapidly by omeprazole than ranitidine. After 2 weeks, daytime epigastric pain was reported by 30% of ranitidine-treated patients but only by 15% of omeprazole-treated patients, which is a statistically significant difference (P = 0.004). No major clinical or biochemical side effects were recorded for either omeprazole or ranitidine. In conclusion, omeprazole 20 mg was found to be superior to ranitidine 300 mg administered once daily for the treatment of duodenal ulcer as measured by ulcer healing and pain relief.

Matched MeSH terms: Duodenal Ulcer/drug therapy*

Fulltext A new concept of the formation of hypoxic cells in tumors and its possible implications for radiotherapy and chemotherapy

Ng CE

Med J Malaysia, 1981 Mar;36(1):24-8.

PMID: 7321933

Hypoxic cells in tumors are proposed to consist of at least 2 types, depending on whether they remain hypoxic for long (chronic hypoxia) or short (acute hypoxia) periods. Experimental evidence of the possible presence ofacutely-hypoxic cells in one type of murine tumour is presented. Finally, the possible implications for radiotherapy and chemotherapy of the presence of acutely-hypoxic cells in human tumors is discussed briefly.

Matched MeSH terms: Neoplasms, Experimental/drug therapy

Displaying publications 241 - 260 of 5160 in total