This article reviews the clinical pharmacokinetics, clinical toxicity and cost-effectiveness analysis of aminoglycosides and of dosing services for aminoglycosides. The reader is referred elsewhere for a review of the pharmacology, antimicrobial spectrum of activity and clinical use of these drugs. A critique of the more commonly used methods of aminoglycoside dosage determinations is included, based on the inter-individual variation in aminoglycoside disposition parameters. The advantages and disadvantages of arbitrary, predictive, and pharmacokinetic methods of dosing determination are summarized. Justification for the routine determination of serum aminoglycoside concentrations is reviewed. We review the lack of standardization of definitions for aminoglycoside-associated nephrotoxicity in published studies, and studies which illustrate these differences are highlighted. Evidence for the association between serum aminoglycoside concentrations and nephrotoxicity is examined. Ototoxicity is similarly reviewed. The concept of cost-effectiveness analysis is examined extensively in this review. We discuss the literature concerning the cost benefit analysis of drug dosing services.
We reviewed our data from 122 records of patients taking phenytoin for the treatment of various types of epilepsy and selected 15 (age range 10-43 years old) who were on phenytoin alone to calculate Michaelis-Menten pharmacokinetic parameters. The average Vm and Km for this age group was found to be 8.45 mg/kg/day and 6.72 mg/litre, respectively. Km was independent of age and weight. Vm correlated well with weight but there was no relationship with age.
This study examined out-patients' interpretation of prescription instructions at a community hospital. The results showed a wide range of misinterpretation with respect to drug name, dose schedule, and auxiliary labels. Age level, education and financial status emerged as the most significant variables associated with the patient's response. Therefore, both physicians and pharmacists may wish to review their traditional prescribing and dispensing procedures to help out-patients make better use of potent medication.
In a 6-month study period, 170 pharmacist interventions in an intensive care unit (ICU) were analysed. Of the interventions, 68.8% were solicited and 31.2% were initiated by the pharmacists. The majority of the interventions were initiated by specialists (69.4%) followed by the medical officers (15.9%) and nurses (9.4%). Most of the interventions occurred during the grand rounds (75.9%), followed by ward visits (12.9%) and communication through the satellite pharmacy (10.5%). The most frequent type of intervention made was for indication or therapeutic efficacy followed by general product information, drug regimen, laboratory assessment, disease state, pharmaceutical availability and adverse drug reaction or side effect. It was also found that 83.7% of pharmacists' suggestions were accepted, 6.4% were accepted with changes, and 9.9% were not accepted. The majority of the interventions were made by direct verbal communications followed by telephone and written communications. In conclusion the study indicates that pharmacist therapeutic recommendations form an important integral element of patient care in an ICU.
We used OPT to estimate individual and population pharmacokinetics for carbamazepine (CBZ) in Malaysian epileptic patients attending our Neurology Clinic. We noted that plasma CBZ concentrations and clearances correlated poorly with daily doses and body weights respectively but we found the values for clearance, volumes of distribution, elimination rate constants and half lives to be in good agreement with earlier reports. We conclude that OPT is a simple yet useful program to derive individual and population pharmacokinetic parameters for CBZ for use in dosage adjustments. We also conclude that although the Malaysian population do not differ substantially in handling CBZ, available data for the pharmacokinetic parameters must be used cautiously in applying it to the therapeutic drug monitoring for CBZ in our patients.
This survey explored patient-orientated services, beyond processing of prescriptions and dispensing of medications, provided by the Malaysian community pharmacist. The results revealed a trend towards the provision of such activities. Although this was not widely implemented by the pharmacists, activities such as patient counselling and providing drug information were part of their daily practice. Lack of time, large workload, and inadequate drug information sources were the constraints cited by the pharmacists for the provision of such activities. If willingness and abilities to perform such activities were the significant barriers, then educational programmes should be initiated to provide the missing competencies.
We estimated individual and population Michaelis-Menten pharmacokinetic parameters for phenytoin (DPH) in epileptic patients attending our neurology clinic using the computer programme. OPT. Our results agreed well with literature values but were lower than those we obtained earlier in a smaller number of patients. The Km was independent of age, weight and sex but there was a weak, correlation between Vm and body weight. We conclude that the use of population Vm and Km in normograms could lead to errors in DPH dose estimations as they correlated very poorly with patient characteristics. OPT was easy to use and sufficiently accurate for deriving dose estimates in routine patients. Its use would enable practitioners to generate their patients' own parameters for use in individual dosage adjustments. The estimates can subsequently be updated as more data become available.
In 1984 a therapeutic drug monitoring (TDM) service was established in Hospital Universiti Sains Malaysia (HUSM) and gentamicin concentrations were measured and used to design optimal regimens for the antibiotic. In this study we report on a 6-year follow-up audit since our first assessment of the service.
To determine how nurses handled drug-related questions in the work environment of a teaching hospital in Malaysia and the type of information sources they used.
Although they originated from China, Malays have undergone a lot of intermarriages. A study suggested that CYP2D6 poor metabolism (PM) phenotype was more common in Malays compared to Chinese. CYP2D6 is highly polymorphic and is involved in the metabolism of many drugs and has been implicated in some environmentally-induced diseases. It is therefore useful to further study this polymorphism in Malays.
Although Malays shared an origin with Chinese, their evolution saw substantial divergences. Phenotyping studies suggested that they differed in CYP2D6 polymorphism, with higher PM prevalence but lesser right-shift for debrisoquine MRs.
Although Malaysian Chinese share an origin with the mainland Chinese, their evolution has been influenced by intermarriages. With a gene such as CYP2D6, which is highly polymorphic, it is expected that the Malaysian Chinese would exhibit a polymorphism profile different from those of the Chinese populations in other geographical locations.
Polymorphism of the beta2-adrenergic receptor (beta2 AR) gene is an important determinant of the function of this receptor. It affects receptor down-regulation and beta2-agonist responses. It has also been a focus of interest in attempts to elucidate the genetic basis of asthma, hypertension, obesity and cystic fibrosis. Several different techniques have been established to determine beta2 AR genotypes but none of these methods are simple enough to detect simultaneously all the five alleles of our research interest (Arg16/Gly16, -20T/C, Gln27/Glu27, -47T/C and Thr164/Ile164).
We hypothesized that as the use of herbal medicines increases in the general population, so do patients' requests to physicians for recommendations. However, why some physicians recommend herbal medicines while others do not is not well understood.
Although the kinetic behaviour of tramadol has been described, the present study is the first to our knowledge, to report specifically on the population pharmacokinetic modelling of tramadol hydrochloride.
BACKGROUND: Cardiovascular diseases are complex diseases that are influenced by both environmental and genetic factors. CYP2D6 found in the brain and the heart is involved in the metabolism of many environmental and some endogenous substances and neurotransmitters responsible for maintaining homeostasis. This raises an interesting hypothesis that it may have a role in the development of or protection against cardiovascular diseases.
OBJECTIVE: To study the distribution of genotypes of CYP2D6 among patients with cardiovascular diseases in Malaysia.
METHOD:We obtained DNA from 128 patients who were followed up for cardiovascular diseases. Polymerase chain reaction-based methods were used to determine common CYP2D6 alleles.
RESULTS: One hundred and twenty-eight patients were enrolled. Most of the patients also had concurrent illnesses. Eleven genotypes were identified in the patients and 41% carried CYP2D6*1/*10. The second most common genotype was homozygous for the wild type gene, followed by homozygous CYP2D6*10/*10 at 14.48 %. A small percentage of the patients were heterozygous CYP2D6*1/*4. One patient was genotyped homozygous CYP2D6*4/*4 predicting a poor metabolizer prevalence of 0.78% (95% CI +/- 1.52%). Analysis using Hardy-Weinberg equilibrium showed that all of the gnotypes were consistent with equilibrium except for CYP2D6*1/*10 (chi(2); P < 0.05).
CONCLUSION: Our study suggests a possible involvement of CYP2D6 genotypes in cardiovascular system diseases, which need to be validated by further studies.
CYP2C8 is genetically polymorphic. Four variants, CYP2C8*2, CYP2C8*3, CYP2C8*4 and CYP2C8*5, which contain mutations in the coding regions have been reported to exhibit different enzyme activity as compared with CYP2C8*1.
CYP2D6 polymorphisms are well described in normal populations but there are few data on its clinical significance. We therefore investigated the influence of CYP2D6 polymorphism on steady-state plasma concentrations and apparent oral clearance of metoprolol in patients with cardiovascular diseases.
CYP2C9 is one of the major drug metabolizing enzymes for many drugs including warfarin, NSAIDs and losartan. It is polymorphic in many populations. Data on the distribution of CYP2C9 and the implication of CYP2C9 polymorphism in the Malaysian population is lacking. Our objectives were therefore to investigate the prevalence of CYP2C9 variants among unrelated healthy volunteers of Malays, Chinese and Indians in Malaysia.
Seventeen single nucleotide polymorphisms (SNPs) have been identified so far, within the beta-2 receptor (beta(2) AR) gene. The presence of so many SNPs within the beta(2) AR gene causes a problem, for those studying beta(2) AR pharmacogenetics, in relation to which SNPs to choose. Most of the work has focused on the three common SNPs within the coding block (alleles 16, 27 and 164) and the techniques developed have been for these three functionally important alleles.