Abstract: Background: Melanocortin-4 receptor (MC4R) is an important regulator of body weight and energy intake. Genetic polymorphisms of the MC4R gene have been found to be linked to obesity in many recent studies across the globe. Aim: This study aimed to examine the effects of MC4R polymorphisms on obesity parameters, Linkage disequilibrium (LD) pattern and haplotypes in Malaysian Malays. Methods: The study subjects were 652 Malaysian Malays. Genomic DNA was extracted from buccal swabs. Genotyping was performed using Sequenom MassARRAY((R)) iPLEX platform. Anthropometric and blood lipid profiles were measured. Results: MC4R rs571312 SNP was associated with logBMI (p = 0.008) and systolic blood pressure (p = 0.005), while MC4R rs2229616 SNP was associated with total cholesterol (TC) levels (p = 0.016). The MC4R rs7227255 SNP did not show any association with obesity parameters. Conclusions: The strength of LD of the MC4R gene region is low and the haplotypes were not associated with obesity in Malaysian Malays.
Abstract: The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D’ = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.
Notes: Apalasamy, Y D xD;Ming, M F xD;Rampal, S xD;Bulgiba, A xD;Mohamed, Z xD;ENG xD;2012/08/23 06:00 xD;Braz J Med Biol Res. 2012 Aug 23. pii: S0100-879X2012007500134.
Abstract: It is proposed that overexpression of P-glycoprotein (P-gp), encoded by the ABC subfamily B member 1 (ABCB1) gene, is involved in resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation and haplotype patterns are population specific which may cause different phenotypes such as response to AEDs. Although several studies examined the link between the common polymorphisms in the ABCB1 gene with resistance to AEDs, the results have been conflicting. This controversy may be caused by the effect of some confounders such as ethnicity and polytherapy. Moreover, expression of the ABCB1 gene is under the control of pregnane X receptor (PXR). Evidence showed that PXR gene contribute to the response to treatment. The aim of this study was to assess the association of ABCB1 and PXR genetic polymorphisms with response to the carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in epilepsy. Genotypes were assessed in 685 Chinese, Indian, and Malay epilepsy patients for ABCB1 (C1236T, G2677T, C3435T) and PXR (G7635A) polymorphisms. No association between these polymorphisms and their haplotypes, and interaction between them, with response to treatment was observed in the overall group or in the Chinese, Indian, and Malay subgroups. Our data showed that these polymorphisms may not contribute to the response to CBZ or VPA monotherapy treatment in epilepsy. (C) 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Notes: Haerian, B. S. Lim, K. S. Mohamed, E. H. M. Tan, H. J. Tan, C. T. Raymond, A. A. Wong, C. P. Wong, S. W. Mohamed, Z.
Abstract: Approximately one third of newly treated epilepsy patients do not respond to antiepileptic drugs (AEDs). Overexpression of P-glycoprotein (P-gp) efflux transporter has been proposed to have a critical role in causing resistance to AEDs. P-gp is a product of the ATP-binding cassette subfamily B member 1 (ABCB1) gene. The purpose of this study was to investigate a possible link between ABCB1 rs3789243 C > T, Cl 2361, G2677T/A, rs6949448 C > T, and C3435T haplotypes with response to carbamazepine (CBZ) or sodium valproate (VPA) monotherapy in Malaysian epilepsy patients. No ABCB1 haplotype association was found with response to either CBZ or VPA monotherapy in the Chinese, Indian, and Malay patients. C3435 allele carriers of the Indian males with cryptogenic epilepsy were more prone to resistance to either CBZ or VPA than carriers of T allele. Moreover, rs37892431 allele carriers of Malay females with symptomatic epilepsy were more resistant to either CBZ or VPA than C allele carriers. Our findings suggest that the ABCB1 rs3789243 C > T, C1236T, G2677T/A, rs6949448 C > T, and C3435T haplotypes do not contribute to response to AED treatment in epilepsy. (C) 2011 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.
Notes: Haerian, B. S. Lim, K. S. Mohamed, E. H. M. Tan, H. J. Tan, C. T. Raymond, A. A. Wong, C. P. Wong, S. W. Mohamed, Z.
Abstract: Recent findings have shown that the rs1042714 (Gln27Glu) single-nucleotide polymorphism (SNP) on the β2-adrenoceptor gene may predispose to obesity. The findings from other studies carried on different populations, however, have been inconsistent. The authors investigated the association between the rs1042714 SNP with obesity-related parameters. DNA of 672 Malaysian Malays was analyzed using real-time polymerase chain reaction. Univariate and multivariate linear regression analyses revealed significant associations between rs1042714 and diastolic blood pressure in the pooled Malaysian Malay subjects under additive and recessive models. After gender stratification, however, a significant association was found between the rs1042714 and triglyceride and the rs1042714 and log-transformed high-density lipoprotein cholesterol levels in Malaysian Malay men. No significant association was found between the SNP and log-transformed body mass index. This polymorphism may have an important role in the development of obesity-related traits in Malaysian Malays. Gender is an effect modifier for the effect of the rs1042714 polymorphism on obesity-related traits in Malaysian Malays. xD;
Abstract: Aims: Several studies demonstrated a link between ABCB1 gene variants and the response to treatment in epilepsy, but the results have been inconclusive. Here, we performed the first haplotype meta-analysis to examine the association of haplotypes of ABCB1 common variants with the response to treatment in epilepsy. Materials & methods: We meta-analyzed the studies that evaluated the role of ABCB1 C1236T, G2677T/A and C3435T polymorphisms and their haplotypes in the response to treatment. Results: Meta-analysis of 23 studies (7067 patients) showed no significant association of ABCB1 alleles, genotypes and haplotypes with the response to treatment in the overall population or in each ethnicity subgroup. Conclusion: Our data suggest that the haplotypes of these loci may not be involved in the response to treatment.
Notes: Haerian, Batoul Sadat Lim, Kheng Seang Tan, Chong Tin Raymond, Azman Ali Mohamed, Zahurin
Abstract: Introduction: The functional point mutation C677T in the methylenetetrahydrofolate reductase (MTHFR) gene, has been reported to contribute to hyperhomocysteinaemia which is a risk factor for atherothrombotic ischaemic strokes. This study evaluated the prevalence of the C677T polymorphism of the gene in Malaysian ischaemic stroke subjects of Malay, Chinese and Indian ethnicities, and its association with homocysteine levels (tHcy). Materials and Methods: A total of 292 subjects were recruited, comprising 150 ischaemic stroke patients and 142 control subjects who were age and sex matched. Plasma homocysteine, serum folate and vitamin B12 were measured in all subjects. Genotyping was carried out using PCR-RFLP. Results: The homocysteine levels were signifi cantly higher (P = 0.001) in the stroke group (11.35 ± 2.75 μmol/L) compared to the control group (10.38 ± 2.79 μmol/L). The MTHFR C677T genotype distribution for the stroke group was 46%, 40% and 14%, respectively for CC, CT and TT genotypes and 59.9%, 33.8% and 6.3%, respectively for the control group. The genotype and allelic frequencies were signifi cantly different between the 2 groups, with P = 0.02 and P = 0.004 respectively. No signifi cant difference was seen in the genotype distribution inter-ethnically. An increasing tHcy was seen with every additional T allele, and the differences in the tHcy for the different genotypes were signifi cant in both the control (P <0.001) and stroke groups (P <0.001). Conclusion: This study shows that TT genotype of the methylenetetrahydrofolate reductase C677T polymorphic gene is an important determinant for homocysteine levels in Malaysian ischaemic stroke patients.
Abstract: Over-expression of P-glycoprotein, encoded by the ABCB1 gene, is proposed to be involved in resistance to antiepileptic drugs in about 30% of patients with epilepsy. Here, we investigated the possible association between ABCB1 polymorphisms and sodium valproate (VPA) treatment in Malaysian epilepsy patients. Genotypeswere assessed in 249 drug-resistant and 256 drug-responsive Malaysian patients for C1236T, G2677T/A, and C 5T polymorphisms in the ABCB1 gene. No genotypes, alleles, or haplotypes were associated with the response to VPA in either the overall group or Chinese, Indian, and Malay subgroups. Our data suggest that C1236T, G2677T/A, and C3435T polymorphisms in the ABCB1 gene do not contribute to the response to VPA in patients with epilepsy.
Notes: Haerian, Batoul Sadat Lim, Kheng Seang Tan, Hui Jan Mohamed, Elsa Hanifa Mejia Tan, Chong Tin Raymond, Azman Ali Wong, Chee Piau Wong, Sau Wei Omar, Haslyna Roslan, Harun Mohamed, Zahurin xD;1
Abstract: The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with the liquid chromatography-mass spectrometry method, this method has shown to be a fast and cost-effective way to perform CYP inhibition studies. The results indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6, with apparent half-maximal inhibitory concentration (IC(50)) values of 0.78 mu g/mL and 0.636 mu g/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC(50) of 39 mu g/mL, and weak inhibition was detected for CYP2C19. The IC(50) of CYP2C19 could not be determined, however, because inhibition was <50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition assay, whereas non-competitive inhibition was shown in inhibition assays using CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4), tranylcypromine (CYP2C19) and furafylline (CYP1A2) were used as positive controls throughout the experiments. This study shows that MSE may contribute to an herb-drug interaction if administered concomitantly with drugs that are substrates for CYP3A4, CYP2D6 and CYP1A2.
Notes: Kong, Wai Mun Chik, Zamri Ramachandra, Murali Subramaniam, Umarani Aziddin, Raja Elina Raja Mohamed, Zahurin
Abstract: Background: Rifampicin is a semisynthetic antibiotic derivative of rifamycin used worldwide for the treatment of various forms of tuberculosis. Objective: The objective of this study was to compare, under fasting conditions in healthy volunteers, the rate and extent of absorption of a generic rifampicin capsule in oral dosage form versus the proprietary equivalent formulation for the purpose of registration approval of the test formulation. Methods: This was an open-label, randomized, 2-treatment, 2-way crossover study with an 8-week washout period between the 2 study arms. Healthy volunteers received a 300-mg capsule of the test formulation (Idaman Pharma Manufacturing Sdn. Bhd.) or two 150-mg capsules of the reference formulation. Blood samples were collected predose and at 45 minutes and 1.25, 1.5, 2, 2.25, 2.5, 3, 3.5, 4, 6, 8, 10, 12, and 24 hours postdose. Plasma concentrations of rifampicin and its metabolite, 25-desacetyl rifampicin, were analyzed using a validated HPLC method. The formulations were considered bioequivalent if the 90% CIs for C(max) and AUC were within the predetermined bioequivalence range (80%-125%, according to the guidelines of the US Food and Drug Administration, or 75%-133% for C(max) only, as set by the European Commission European Medicines Agency and the National Pharmaceutical Control Bureau of Malaysia). Tolerability was assessed by verbally questioning subjects regarding their well-being and any feelings of discomfort. All events reported by the subjects (serious or mild) were recorded on adverse-event forms. Results: Fourteen healthy subjects (10 males, 4 females) with a mean age of 22.6 years (range, 20-28 years) and a mean body mass index of 22.2 kg/m(2) (range, 18.3-29.9 kg/m(2)) were enrolled in the study; all 14 completed the trial as outlined in the protocol. The mean values for C(max), T(max), AUC(0-24), and AUC(0-infinity) with the test formulation of rifampicin were 7.20 mu g/mL, 1.32 hours, 37.12 mu g/mL . h, and 39.69 mu g/mL . h, respectively; for the reference formulation, the values were 7.65 mu g/mL, 1.71 hours, 38.92 mu g/mL . h, and 42.24 mu g/mL . h. For 25-desacetyl rifampicin, the mean values for C(max), T(max), AUC(0-24), and AUC(0-infinity) with the test formulation were 0.63 mu g/mL, 3.45 hours, 4.92 mu g/mL . h, and 6.27 mu g/mL . h; for the reference formulation, the values were 0.7 mu g/mL, 3.27 hours, 5.23 mu g/mL . h, and 6.84 mu g/mL . h. For rifampicin, the 90% CIs for the test formulation/reference formulation ratio for the logarithmic transformations of both C(max) and AUC(0-infinity). were within the bioequivalence limit of 80% to 125% (80.9-109.7 and 80.7-103.2, respectively). For 25-desacetyl rifampicin, the 90% CI for the test formulation/reference formulation ratio for the logarithmic transformations of AUC(0-24) (80.0-104.7) was within the bioequivalence limit of 80% to 125%. However, the 90% CI for C(max) (78.4-102.2) was outside this limit but still within the acceptance limit for C(max) when adhering to the bioequivalence range of 75% to 133%. No adverse events were reported during the study. Conclusions: This study found that the 300-mg test capsule and the 150-mg reference capsules of rifampicin met the regulatory criteria for assuming bioequivalence in these fasting healthy volunteers. Both formulations appeared to be well tolerated in the population studied. (Clin Ther. 2010;32:1822-1831) (C) 2010 Excerpta Medica Inc.
Abstract: A sensitive and simple Gas Chromatographic-Mass Spectrometric method was developed and validated for the determination of captopril in human plasma. Thiosalicylic acid was used as an internal standard, and plasma extraction was performed by solid phase extraction. The limit of quantification was 0.5 ng/mL with signal to noise ratio greater than 5. The calibration curve was linear from 1 to 160 ng/mL with r(2) greater than 0.99. The coefficient of variation for within and between assay imprecision of the standards and for the limit of quantification were <= 10 % and <= 7 %, respectively. The percentage of inaccuracy for within-and between-assay including lower and upper limits of quantitation were < 8 % and <= 6 %, respectively. The absolute recovery of captopril and thiosalicylic acid in plasma were greater than 98 % and 99 %, respectively. The high sensitivity and accuracy of this method allowed us to measure low concentrations of captopril in plasma for bioequivalence studies in healthy subjects.
Notes: Chik, Z. Mustafa, A. M. Mohamed, Z. Lee, T. C.
Abstract: Over-expression of P-glycoprotein (P-gp), the encoded product of the ATP-binding cassette (ABC), sub-family B, member 1 (ABCB1/MDR1) gene, plays an important role in mediating multidrug resistance to antiepileptic drugs (AEDs) in about 30% of patients with epilepsy. Genetic variation may in part explain inter-individual differences in phenotype-genotype relationships in the pharmacological response of epilepsy patients to AEDs. The synonymous C3435T polymorphism is one of the most common allelic variants in the ABCB1/MDR1 gene, proposed in the causation of refractory epilepsy. Many studies have shown the relationship between C3435T polymorphism and refractoriness to AEDs in epilepsy. However, there is controversy between the findings of various studies, that is, whether ABCB1/MDR1 C3435T gene polymorphism is associated with response to AEDs in epilepsy patients. This review provides a background and discusses the results of investigations on possible confounding factors affecting the interpretation and implementation of association studies in this area.
Abstract: Aims: Impaired S-mephenytoin 4′-hydroxylation is a well-described genetic polymorphism affecting drug metabolism in humans. Although ethnic differences in its distribution of polymorphism has been described, it is not known whether there is an ethnic heterogeneity of the structure and expression of the CYP2C19 enzyme in the Malaysian population. Methods: Study subjects were 142 healthy, unrelated Malaysians aged 18-29 years. Baseline omeprazole and 2-h postingestion omeprazole and 5′-hydroxyomeprazole concentrations were measured for CYP2C19 phenotype determination. Identification of CYP2C19 genotypes was performed with the use of polymerase chain reaction. Results: Phenotyping of CYP2C19 revealed that the prevalence of poor metabolizers (PMs) in the Malaysian population was 14.1%, whereas prevalence of PMs in genotyping was 12.6%. The PM genotypic prevalence rate was 5.6% in Malays, 19.1% in Chinese and 10.0% in Indian subjects. There were significant differences in PM genotypic prevalence rates among the three primary ethnic groups (P ≤ 0.05). Conclusions: Phenotyping and genotyping revealed significant differences in the prevalence rates among the three ethnic groups in Malaysia, with Chinese recording highest prevalence.
Abstract: Aims Nafcillin (Wyeth Laboratories, Philadelphia, PA, USA) has been reported to induce the metabolism of cyclosporin and warfarin, which are known substrates of cytochrome P-450 (CYP). However, there has not been any report to date on its possible interaction with nifedipine, an index substrate of the enzyme, CYP3A4. Methods Nine healthy normotensive subjects participated in this randomized placebo-controlled two-way crossover study examining the effects of 5 days' pretreatment of nafcillin 500 mg or placebo four times daily on the pharmacokinetics of an oral dose of nifedipine 10 mg. Plasma nifedipine concentrations were measured by gas chromatography-mass spectro. Results The area under the plasma nifedipine concentration-time curve (AUC(0-alpha)) in nafcillin-pretreated subjects (80.9 +/- 32.9 mug l(-1) h(-1)) was significantly decreased compared with subjects who received only nifedipine (216.4 +/- 93.2 mug l(-1) h(-1) ) (P < 0.001). Total plasma clearance of nifedipine (CL/F) was significantly increased with nafcillin pretreatment (138.5 +/- 42.0 l h(-1) vs 56.5 +/- 32.0 l h(-1) ) (P < 0.002). Conclusions The results show that nafcillin pretreatment markedly increased the clearance of nifedipine and suggest that nafcillin is a potent inducer of CYP enzyme.
Notes: Lang, CC Jamal, SK Mohamed, Z Mustafa, MR Mustafa, AM Lee, TC
Abstract: A comparative randomized crossover study was conducted to determine the pharmacokinetics of theophylline in male and female camels (Camelus dromedarius) and goats (Caprus hircus). Theophylline is an established 'probe drug' to evaluate the drug metabolizing enzyme activity of animals. It was administered by the intravenous (i.v.) route and then intramuscularly (i.m.) at a dose of 2 mg/kg. The concentration of the drug in plasma was measured using a high-performance liquid chromatography (HPLC) technique on samples collected at frequent intervals after administration. Following i.v. injection, die overall elimination rate constant (lambda(z)) in goats was 0.006 +/- 0.00076/min and in camels was 0.0046 +/- 0.0008/min (P < 0.01). The elimination half-life (t(1/2lambdaz)) in goats (112.7 min) was lower than in camels (154.7 min) (P < 0.01). The apparent volume of distribution (V-z) and the total body clearance (Cl) in goats were 1440.1 +/- 166.6 ml/kg and 8.9 +/- 1.4 ml/min/ kg, respectively. The corresponding values in camels were 1720.3 +/- 345.3 ml/kg and 6.1 +/- 1.0 ml/ min/kg, respectively. After i.m. administration, theophylline reached a peak plasma concentration (C-max) of 1.8 +/- 0.1 and 1.7 +/- 0.2 mug/ml at a post-injection dine (T-max) of 67.5 +/- 8.6 and 122.3 +/- 6.7 min in goats and camels, respectively. The mean bioavailability (F) in both goats and camels was 0.9 +/- 0.2. The above data suggest that camels eliminate theophylline at a slower rate than goats.
Notes: ISI Document Delivery No.: 510AA xD;Times Cited: 2 xD;Cited Reference Count: 24 xD;Elsheikh, HA Ali, BH Zahurin, M Mustafa, AM Alhadrami, G Bashir, AK xD;Blackwell verlag gmbh xD;Berlin
Abstract: This study investigates the pharmacokinetics of gentamicin in newborns in the Special Care Nursery in University Hospital. They were divided into 3 groups according to gestational age: Group I, 26 to 30 weeks (n=10), Group II, 31 to 35 weeks (n=27), and Group III, 36 to 40 weeks (n=36). Each subject received 2.5mg/kg gentamicin (gentamicin sulphate, David Bull) every 12 h initially. The pharmacokinetic parameters for each newborn were derived from the measured plasma C max and C min levels taken at steady state, according to the Sawchuk-Zaske method. The subsequent dosage regimen was calculated using these parameters. Gentamicin trough levels in the newborn ranged from 0.57 to 4.94 m̈g/mL while the peak levels ranged from 4.24 to 12.42 m̈g/mL. The apparent volume of distribution (V d) (means ± SEM) increased with gestational age, the V d being 0.81 ± 0.09, 1.00 ± 0.06 and 1.49 ± 0.06 L for groups I, II and III respectively. The differences between the groups were significant (P<0.01; Student's t-test). There was an observable decrease in t 1/2 with increasing gestational age, the t 1/2 (mean ± SEM) being 10.02 ± 1.19 h, 8.53 ± 0.38 h and 7.10 ± 0.31 h for Groups I, II and III respectively. This decrease in the t 1/2 was accompanied by a similar increase in CL (0.07 ± 0.02,0.09 ±0.01 and 0.15 ±0.011/h for Groups I, II and III respectively). The changes in t 1/2 and CL were significant (P<0.01) between Groups I and III, and between Groups II and III. These findings show that differences exist in the pharmacokinetic parameters of newborns when grouped according to gestational age. For the effective monitoring of gentamicin especially with regard to the initial estimation of drug dosage, the appropriate set of pharmacokinetic parameters should be used for the newborn of that gestational age. (JUMMEC 1997 2(1): 35-38).
Abstract: Dextromethorphan (DM) is O-demethylated to its main metabolite, dextrorphan (DO), following a polymorphic reaction that depends on the isoenzyme, cytochrome P4502D6 (CYP2D6). Traditionally, phenotyping of this isoenzyme utilises debrisoquine, individuals with rapid or normal metabolism of debrisoquine are described as "extensive metabolisers" and those with slower drug metabolism are known as "poor metabolisers". Drug oxidation phenotyping with DM has been found to be in complete concordance with results of phenotyping with debrisoquine. A sensitive High Performance Liquid Chromatography method with both fluorescent and UV detection was developed for the analysis of DM and DO in human urine. Prior to analysis by HPLC, the urine samples were subjected to enzymatic hydrolysis of the dextrorphan glucuronides followed by extraction into chloroform:isopropanol mixture. Standard curves for both compounds were linear over concentrations ranging from 0 to 500 ng/ml with a mean linear regression value of 0.98 for DM and 0.97 for DO. The intra-assay error was 4.07% and 7.05% for DM and DO respectively and the interassay error was 18.16% and 7.13% for DM and DO respectively. Following ingestion of 15 mg dextromethorphan hydrobromide, a preliminary oxidation phenotyping was performed on 8 volunteers. The metabolite ratio was calculated as MR = 0-8 hr urinary output of unchanged DM/0-8 hr urinary output of DO. The total urinary output of DM ranged from 0 to 4.87 mg whereas that of DO ranged from 0.57 to 21.00 mg. The MR values were between 0 to 0.220 in 7 of the subjects tested while 1 subject showed a relatively high MR value of 1.376. This was consistent with the finding that in this same subject the urinary output of DM was the highest, and the output of DO was the lowest among those tested, thus indicating that this subject is possibly a poor metabiliser of DM. It is concluded that the assay is sensitive for the measurements of levels of DM and DO in human urine and hence will be utilised in a large scale study of the frequency distribution of drug oxidation phenotyping with DM in a Malaysian population. (]UMMEC 1997 2(1):22-25).
Abstract: Surgery on the upper limb can be performed under axillary block of the brachial plexus. Bupivacaine is often used as the local anaesthetic. To determine whether recommended doses are appropriate for the local population, venous plasma bupivacaine concentrations were measured after axillary block in 14 Malaysian patients. Plasma bupivacaine was assayed by high-performance liquid chromatography. With a dose range of 60-160 mg or 1.7-3.0 mg kg(-1) (126 +/- 30 mg or 2.2 +/- 0.4 mg kg(-1), respectively, mean +/- SD) peak plasma concentrations of 0.72-3.65 mu g ml(-1) were obtained. There was a wide scatter of individual values. Peak concentrations occurred at about 20 min. These levels were in concurrence with other published studies. We conclude that at a dose range of up to 3.0 mg kg(-1) in our patients, the plasma levels reached did not result in those associated with developing clinical symptoms or signs of toxicity.
