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C Adithan

Publications and source records attributed to C Adithan.

At least 19 recordsLinked to original sources
PubMed2006

Common variants of Cholesteryl ester transfer protein gene and their association with lipid parameters in healthy volunteers of Tamilian population.

BACKGROUND: Cholesteryl ester transfer protein (CETP) is involved in a key pathway of reverse cholesterol transport implicated in atherosclerosis and coronary heart disease. CETP gene is known to have many single nucleotide polymorphisms which have been associated with CETP activity and plasma high density lipoprotein cholesterol (HDL-C) concentrations. No data on the prevalence of these polymorphisms and their phenotypic association is available in South Indian population. METHODS: Three CETP polymorphisms: TaqIB, -629C/A and I405V were studied in 171 healthy volunteers from Tamilnadu, a major population of South India. Subjects were clinically examined and lipid profile was estimated. Genotyping was performed by PCR-RFLP and genotype frequencies estimated. RESULTS: The allele frequencies of TaqIB: B1 allele was 0.51; -629C/A: C allele was 0.36; and that of I405V: I allele was 0.47. Study of association between these three polymorphisms and plasma lipid concentrations revealed no significant differences in lipid parameters between genotypes. A gender based subgroup analysis revealed a significant increase in HDL-C in men with B2B2 genotype and decrease in TG in B1B2 genotype. Analysis of the combined effect of multiple mutant genotypes revealed that as the number of mutant genotypes increased, the concentrations of low density lipoprotein-cholesterol (LDL-C), HDL-C and total cholesterol (TC) increased whereas that of triglyceride (TG) decreased in the group of three mutant genotypes significantly. CONCLUSION: The frequency of B2 and A alleles of TaqIB and -629C/A polymorphisms were highest in Tamilian population when compared to other major ethnic groups while that of V allele of I405V polymorphism is between Caucasians and African Americans. Taq1B polymorphism was associated with HDL-C and TG concentrations only in men. Combination of these three polymorphisms was significantly associated with lipid profile than the individual polymorphisms.

Cholesterol Ester Transfer Proteins↗
PubMed2006

Influence of the CYP2C9 AND CYP2C19 polymorphisms on phenytoin hydroxylation in healthy individuals from south India.

BACKGROUND AND OBJECTIVES: Phenytoin, a widely used anti-epileptic drug, is metabolized mainly by CYP2C9 (90%) and partly by CYP2C19 (10%) to its major metabolite 5-(para-hydroxyphenyl)-5- phenylhydantoin (p-HPPH). The CYP2C9 and CYP2C19 genes encoding these enzymes are polymorphically expressed and most of the variants result in decreased metabolism of the respective substrates. The present study was undertaken to investigate the influence of the CYP2C9*2 and *3 as well as CYP2C19*2 and *3 variant genotypes on phenytoin hydroxylation in healthy subjects from south India. METHODS: A total of 27 healthy, unrelated, subjects were administered a single oral dose of 300 mg phenytoin. Four hours later, 5 ml of blood was collected and genotyped for CYP2C9*1, *2, *3, CYP2C19*1, *2 and *3 by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Phenytoin and the major metabolite p-HPPH were estimated by reverse phase HPLC. The metabolic ratio was calculated as concentration of phenytoin/p-HPPH. RESULTS: A significant correlation was observed between the CYP2C9 genotype and metabolic ratio of phenytoin/p-HPPH (r = 0.472, 95% CI 0.100 to 0.728; P = 0.01). While no association was found with CYP2C19 alone, a significant correlation was observed between the combined CYP2C9 and CYP2C19 genotypes and phenytoin metabolic ratio (r = 0.507, 95% CI 0.146 to 0.749; P< 0.01). INTERPRETATION AND CONCLUSION: CYP2C9*2 and *3 mutant alleles caused decreased hydroxylation of phenytoin in vivo, whereas the mutant alleles of CYP2C19 played only a minor role in the metabolism of phenytoin in subjects of our study. The results of present preliminary study needs to be confirmed with a larger sample.

Adult↗
PubMed2005

The effect of the CYP2C19 genotype on the hydroxylation index of omeprazole in South Indians.

To investigate the relationship between CYP2C19 genotypes and the hydroxylation index (HI) of omeprazole in the South Indian population. Healthy unrelated South Indian subjects (n=300) were separated into three groups based on their CYP2C19 genotypes. They were administered a single oral dose of 20 mg omeprazole, and venous blood was collected 3 h later. Plasma was assayed using reversed-phase high-performance liquid chromatography, and the omeprazole HI was calculated. The means of HIs in individuals with CYP2C19*1/*1 (n=124), *1/*2 (n=129) and *2/*2,*2/*3 (n=47) were 2.4, 5.3 and 22.5, respectively, and were found to be significantly different between any two groups (P<0.0001). A good correlation was established between CYP2C19 genotype and omeprazole HI (r=0.54, 95% CI 0.45-0.62; P<0.0001). Of the 300 subjects, 42 (14.0%; 95% CI 10.1-17.9) were phenotypic poor metabolizers (PMs), but only 33 of them had two mutant alleles and the remaining 9 PMs had at least one wild-type allele. Among the 258 extensive metabolizers, 14 had two mutant alleles. The prevalence of PMs in the South Indian population was 14.0%, which is similar to that in North Indians and Orientals but significantly higher than in Caucasians and Africans. A genotype-phenotype relationship was established between the CYP2C19 genotype and HI of omeprazole, but 7.7% of subjects deviated from expected genotype-phenotype associations. This could be due to an additional mutation, either in the exons/introns or in the 5'-regulatory region of the CYP2C19 gene.

Adult↗
PubMed2004

Glutathione S-transferase M1 and T1 null genotype distribution in South Indians.

OBJECTIVE: To investigate the distribution of the homozygous null genotypes of GSTM1 and GSTT1 in the South Indian population. METHODS: Five hundred and seventeen unrelated natives of the South Indian states of Tamilnadu and Pondicherry (n=170), Kerala (n=122), Karnataka (n=110) and Andhra Pradesh (n=115) were analyzed for homozygous deletions of GSTM1 and GSTT1. A multiplex polymerase chain reaction method simultaneously detected both GSTM1 and GSTT1 homozygous null genotypes. The observed frequencies from the four groups were compared statistically with each other and the combined frequencies were compared with frequencies of other major populations previously reported in the literature. RESULTS: In South India, 30.4% (95% CI 26.4-34.3) lacked the GSTM1 gene, 16.8% (13.6-20.1) lacked the GSTT1 gene and 4.6% (3.0-6.8) lacked both the GSTM1 and GSTT1 genes. The highest frequency of GSTM1 null was observed in Karnataka (36.4%, 27.4-45.4), while Andhra Pradesh had the lowest frequency of the GSTM1 and GSTT1 combined double-null genotypes (1.7%, 0.21-6.2). CONCLUSION: The prevalence of the GSTM1 null genotype differed within India. The frequency of GSTM1 null in South Indians was significantly lower than that in Caucasians. The frequencies of both GSTM1 and GSTT1 null genotypes in South Indians were significantly lower than in the Japanese.

Adult↗
PubMed2003

Allele and genotype frequency of CYP2C9 in Tamilnadu population.

OBJECTIVES: To identify the frequency of CYP2C9*1, *2 and *3 alleles and the genotype of CYP2C9 gene in the Tamilian population. METHODS: The study was conducted on 135 unrelated healthy human volunteers. DNA was extracted from the peripheral leukocytes samples and was analyzed using the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) protocol. The PCR products were digested with AvaII, KpnI or NsiI restriction enzymes. The digested products were separated using 8% polyacrylamide gel and stained by ethidium bromide. Genotyping of the subjects was done based on DNA fragment size. RESULTS: The frequencies of CYP2C9*1, *2 and *3 alleles in the Tamilian population were 0.907, 0.026 and 0.067, respectively. The distribution of CYP2C9*1/*1, *1/*2, *1/*3 and *2/*3 genotypes were 0.823, 0.044, 0.126 and 0.007, respectively. CONCLUSION: CYP2C9*3 is the most frequent mutant allele found in the Tamilian population. The distribution of this mutant allele in the Tamilian population was found to be lesser than in Caucasians but higher than in Chinese.

Adult↗
PubMed2003

Genotype and allele frequency of CYP2D6 in Tamilian population.

OBJECTIVE: To assess the frequency of CYP2D6 *3, *4, *5 and *10 allelic variants in a South Indian population and compare the frequencies with other major populations. METHODS: Polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism (RFLP)-based methods were used to identify the CYP2D6 genotypes of 106 healthy unrelated male and female volunteers of Tamilian origin. The allele and genotype frequencies observed were compared with other major populations. RESULTS: The *10 allele was the most frequent mutant allele in Tamilians (20.3%). The *5 allele occurred at 0.9% and the *3 allele was not detected. The most frequent allele causing enzyme inactivation was *4 allele in Tamilians (6.6%), which is significantly higher than that reported in Japanese (0%). CONCLUSIONS: The *10 allele is the most common mutant allele in Tamilians. The CYP2D6*4 and CYP2D6*5 alleles are distributed in a significantly different way in the Tamil population relative to Oriental populations.

Adult↗
PubMed2003

Allele and genotype frequency of CYP2C19 in a Tamilian population.

AIMS: To investigate the frequencies of CYP2C19*1, CYP2C19*2 and CYP2C19*3 alleles and CYP2C19 genotypes in a Tamilian population. METHODS: The study was conducted in 112 unrelated healthy human volunteers. DNA was extracted from leucocytes and analyzed by the PCR-RFLP protocol. The PCR product was digested with restriction enzymes (SmaI and BamH1) and then separated electrophoretically using polyacrylamide gel. RESULTS: The frequencies of the CYP2C19*1, *2 and *3 alleles were 0.598 [95% confidence interval (CI) 0.507, 0.689], 0.379 (95% CI, 0.350,0.407) and 0.022 (95% CI -0.005, 0.049), respectively. The distribution of CYP2C19*1/*1,*1/*2, *1/*3, *2/*2 and *2/*3 genotypes were 0.295 (95% CI, 0.210, 0.379), 0.580 (95% CI, 0.488, 0.671), 0.027 (95% CI -0.003, 0.057), 0.080 (95% CI 0.030, 0.130) and 0.018 (95% CI -0.006, 0.042), respectively. CONCLUSIONS: The distribution of CYP2C19*1/*1 in the Tamilian population is lower than that in Caucasians, Africans and the North Indian population. The CYP2C19*1/*2 is significantly higher in Tamilians when compared with other populations. The CYP2C19*1/*3 allele, which was not reported in the North Indian and Caucasian populations has been identified in 2.7% of the Tamilian population.

Adult↗
PubMed2002

Effect of honey on carbamazepine kinetics in rabbits.

The study was undertaken to determine the effect of honey on carbamazepine kinetics in rabbits. The study was done on three occasions in each animal. Study 1 was carried out after single dose administration of carbamazepine (80 mg/kg, po), along with saline (2.34 ml/kg, po). After a wash out period of one week, the second study was carried out by co-administration of carbamazepine with honey (2.34ml/kg, po). After this, the animals continued to receive honey (2.34ml/kg, po), once daily, for 7 days. On the eighth day of honey treatment, the carbamazepine kinetics was studied again. Pharmacokinetic analysis revealed that single as well as multiple dose honey treatment showed a significant decrease in area under the plasma time concentration curve (AUC) when compared with saline treated control. A significant increase in the clearance (CL/F) rate of carbamazepine was observed only after multiple dose honey treatment. Both single and multiple dose honey treatment did not show any significant effect on other pharmacokinetic parameters like t1/2, Cmax, Tmax and Vd when compared with saline treated group. Data thus obtained suggested that honey decreases the bioavailability of carbamazepine.

Animals↗
PubMed2002

Influence of honey on orally and intravenously administered diltiazem kinetics in rabbits.

Effect of honey on plasma concentration of diltiazem after oral and intravenous administration in rabbits, has been studied. For oral study, single dose of diltiazem (5 mg/kg, p.o.) along with saline was administered to New Zealand white rabbits (n=8). Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6 and 8 hr after drug administration from marginal ear vein. After a washout period of one week, diltiazem was administered with honey (2.34 ml/kg; p.o.) and the blood samples were collected as above. To the same animals honey (2.34 ml/kg; p.o.) was continued once daily for 7 days. On 8th day, honey and diltiazem were administered simultaneously and blood samples were collected at similar time intervals as mentioned above. For intravenous study the pharmacokinetic was done in each animal on two occasions. The first study was done after single dose administration of diltiazem (5 mg/kg; i.v.) along with saline (2.34 ml/kg; p.o.). Blood samples were collected at 0, 0.083, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4 and 6 hr after i.v. diltiazem administration. The same animals were treated with honey (2.34 ml/kg; p.o.) for seven days. On day 8, the second study was carried out with single dose i.v. administration of diltiazem along with honey (2.34 ml/kg; p.o.) and blood samples were collected. In the oral study, single dose administration of honey decreased the AUC and Cmax of diltiazem associated with significant increase in clearance and volume of distribution when compared to saline treated group. After one week administration of honey, diltiazem kinetic data showed further reduction in AUC and Cmax and increase in clearance and volume of distribution. In the i.v. study also, multiple dose administration of honey significantly reduced the AUC and increased the clearance value of diltiazem. The results suggest that honey may decrease the plasma concentration of diltiazem after its oral or i.v. administration in rabbits.

Administration, Oral↗
PubMed2000

Effect of two types of Indian breakfast on bioavailability of cefuroxime axetil.

BACKGROUND & OBJECTIVES: The oral bioavailability of cefuroxime axetil is enhanced by food. This study was done to compare the effect of two types of Indian breakfast on the bioavailability of cefuroxime axetil in healthy volunteers. METHODS: Eight healthy male volunteers participated in the crossover study. Subjects were randomized to receive either one of the two types of breakfast, Diet-A or Diet-B, 10 min before single dose of 500 mg cefuroxime axetil. After a washout period of one week the study was repeated with the other type of diet. Diet-A included idly with chutney. Diet-B included poori and dal-fry. Blood samples for pharmacokinetic analysis were obtained prior to dosing and at 0.25, 0.50, 0.75, 1.0, 1.5, 2.0, 2.5, 3.0, 4.0, 5.0, 6.0 and 8.0 h following dosing and urine collections were done for 8 h. The serum and urine samples were assayed by using HPLC. RESULTS: The AUC and Cmax were significantly increased after oral administration of cefuroxime axetil with Diet-B, when compared to Diet-A (P < 0.01 and P < 0.02 respectively). The values of apparent absorption rate constant, lag-time, Tmax and t1/2 beta for the two regimens were not significantly different. The volume of distribution and plasma clearance for cefuroxime were significantly lower (P < 0.02, P < 0.001 respectively) in the regimen with Diet-B. The 8 h urinary recovery of cefuroxime was 16.59 and 28.44 per cent (P < 0.005) with Diet-A and Diet-B respectively. INTERPRETATION & CONCLUSIONS: The administration of cefuroxime axetil with poori and dal-fry may enhance the bioavailability when compared with idly and chutney.

Adult↗
PubMed2000

Genetic polymorphism of CYP2D6 in Karnataka and Andhra Pradesh population in India.

AIM: To study the prevalence of cytochrome P-450 2D6 (CYP2D6) polymorphism in Karnataka (KA) and Andhra Pradesh (AP) population. METHODS: Two hundred and eleven healthy human volunteers participated in the study (100 from KA and 111 from AP). At bed time, after voiding their bladder, the volunteers ingested 30 mg of dextromethorphan hydrobromide (DM). Urine samples were collected for 8 h. DM and its metabolite dextrorphan (DT) were estimated in the urine using HPLC. The metabolic ratio (DM/DT) was used for phenotyping. RESULTS: The prevalence of poor metabolisers (PM) in KA is 4% and AP is 1.8%. CONCLUSION: The frequency of PM phenotype in South Indian population is in between the Western and Oriental population.

Adolescent↗
PubMed1995

Cortisol status in different types of leprosy.

Basal plasma cortisol levels in 12 controls and 60 patients with different types of leprosy were within normal limits. They were significantly lower in multibacillary leprosy patients; this abnormality might be due to long standing stress leading to adrenal exhaustion. The plasma cortisol level significantly increased after the ACTH (Synacthen) stimulation test in all of the varieties of leprosy tested, which suggests that the adrenal reserve is maintained in such cases.

Adrenocorticotropic Hormone↗
PubMed1994

IgG subclass response and protection against challenge following immunisation of mice with various influenza A vaccines.

The serum total IgG and IgG subclass and nasal wash IgA and IgG antibody responses of mice to influenza virus A/Hong Kong/68 (H3N2) subunit preparations administered parenterally as a single dose, incorporated either in immune stimulatory compounds (ISCOMs) or liposomes with Freund's Complete Adjuvant, or as an aqueous material, as well as to live, infectious virus were measured by ELISA at 10 days and 3, 5, 7 and 22 weeks after immunisation. The protection of the upper and lower respiratory tracts provided by these preparations against homologous and heterologous challenge infection was assessed. Of the four variously-presented subunit preparations, influenza subunit ISCOMs induced relatively high and persisting levels of each of the different IgG subclasses, particularly IgG2a, throughout the study, and most nearly approached those observed after intranasal infection of mice with infectious virus. Furthermore, nasal wash IgA and IgG antibody levels, particularly at 5 or 7 weeks after immunisation, were also significantly greater in mice given the subunit ISCOM preparation than those induced by other subunit preparations with adjuvant or subunits given alone, and provided protection of both the upper and lower respiratory tracts against challenge as similar to that elicited by infectious virus.

Animals↗
PubMed1992

Altered pharmacokinetics of lignocaine after epidural injection in type II diabetics.

The pharmacokinetics of lignocaine has been compared after epidural anaesthesia in diabetics and non-diabetic patients. Epidural lignocaine 8 mg.kg-1 was given to 8 well controlled Type II diabetic and 8 non-diabetic patients and the plasma drug concentration in serial blood samples were measured by HPLC. The plasma level of lignocaine was lower in diabetics compared to non-diabetics. The peak level was attained at 20 min in both groups. The clearance of the drug was significantly higher, (39.9 vs 16.7 ml.min-1.kg-1) associated with a decreased elimination half-life and mean residence time. The study suggests that the rate of absorption of lignocaine is not altered after epidural administration and that its hepatic metabolism is increased in diabetics compared to non-diabetics.

Adult↗
PubMed1992

Comparative bioavailability of two brands of ciprofloxacin: an Indian study.

A randomized crossover study was carried out to determine the bioavailability of two commercially available brands of ciprofloxacin after oral administration in healthy volunteers. There were no significant differences in the pharmacokinetic parameters that characterize bioavailability between the two brands. It is therefore concluded that there is no bioinequivalence between these ciprofloxacin brands.

Administration, Oral↗
PubMed1992

Pharmacokinetics of single dose oral digoxin in patients with uncomplicated type II diabetes mellitus.

Digoxin pharmacokinetics was studied in eight patients with uncomplicated type II diabetes mellitus and seven healthy volunteers. After a single oral dose of digoxin (1 mg), the drug concentration was measured in the serum collected at different time intervals, using a radioimmunoassay method. The diabetics had a higher serum concentration of drug when compared to control. The clearance rate of digoxin was significantly reduced in diabetics when compared to healthy volunteers. The elimination half-life of about 22 hours in both groups is much less than that reported in Western data. Possible reasons for this discrepancy are discussed.

Administration, Oral↗