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Biomedical subjects

C Prakash

Publications and source records attributed to C Prakash.

At least 37 records · Page 2Linked to original sources
PubMed1999

Botulinum toxin injections for achalasia symptoms can approximate the short term efficacy of a single pneumatic dilation: a survival analysis approach.

OBJECTIVE: Botulinum toxin injection can induce a temporary symptomatic remission in some patients with achalasia, but the comparative utility of the approach is not fully known. This study used survival analysis methods to better understand the ability of single or repeated botulinum toxin injections to postpone the need for other treatments. METHODS: The response to botulinum toxin in 42 patients with idiopathic achalasia who had not received prior treatment was compared with the outcome in 26 consecutive patients who underwent initial treatment with pneumatic dilation. Survival analysis methods were employed using time to retreatment as the principal outcome measure. RESULTS: Retreatment (any type) was required in 50% of subjects at 265 days (0.73 yr) after the first botulinum toxin injection. In contrast, retreatment after initial pneumatic dilation was required in <40% of patients after 2 and 5 yr of follow-up. The curves became significantly separated (p < 0.05) within 1 yr after initial treatment. Of those treated solely with botulinum toxin injections, repeated as needed, only 46% required pneumatic dilation or surgery by 2 yr. Survival analysis curves for repeated injections and initial pneumatic dilation did not differ statistically at 1 or 2 yr (p = 0.5 and p = 0.4, respectively). Correlational analyses indicated that, of the clinical parameters tested, only the degree of dysphagia for liquids was useful in selecting the better responders to botulinum toxin injections, with lesser symptoms predicting longer time to retreatment. CONCLUSIONS: Botulinum toxin injections, repeated as needed, can approximate the benefits of a single pneumatic dilation for < or = 2 yr from the standpoint of usual factors that drive further management.

Botulinum Toxins, Type A↗
PubMed1998

Tricyclic antidepressants for functional nausea and vomiting: clinical outcome in 37 patients.

Tricyclic antidepressants (TCAs) have been used successfully in the treatment of irritable bowel syndrome and unexplained chest pain. Little information is available regarding their use in other functional gastrointestinal disorders. Clinical charts were analyzed from 37 outpatients (mean age 45 +/- 2 years, 25 females/12 males) with chronic nausea and vomiting that could not be explained by any conventional organic disorder (mean duration of symptoms 28 +/- 8 months). Twenty-one (57%) had chronic persistent symptoms; 16 (43%) had intermittent relapsing symptoms; 13 (35%) also had pain as a dominant complaint. Each patient had been treated with TCAs specifically for the gastrointestinal symptoms (amitriptyline, desipramine, nortriptyline, doxepin, or imipramine), and the subject group was followed for 5.4 +/- 1.1 months. Response (at least moderate symptom reduction using a priori chart rating criteria) occurred in 31 patients (84%), and complete symptom remission occurred in 19 (51%)--in 41% with the first TCA trial. Dose at response averaged 50 mg/day, and outcome was unrelated to TCA used. Logistic regression analysis revealed that pain dominance interfered with remission (P = 0.03), but other clinical characteristics were not predictive of outcome. This uncontrolled clinical experience indicates that the open-label response rate of functional nausea and vomiting to low dosages of TCAs resembles that noted in irritable bowel syndrome. TCAs should be studied in controlled fashion for this and related dyspeptic syndromes, as the success of other treatments is limited.

Adult↗
PubMed1998

Acute ileal diverticulitis.

Four cases of acute ileal diverticulitis are presented wherein early diagnosis helped avoid emergent surgery. All patients did well initially with conservative medical management. Acute ileal diverticulitis, although uncommon, should be suspected when the clinical presentation indicates an inflammatory condition of the lower right abdomen. Surgery, when required for recurrent disease, can be reserved for the interval between acute episodes.

Acute Disease↗
PubMed1998

Hepatitis C and hepatitis E in acute sporadic non-A non-B hepatitis in hospital patients of Delhi (India).

Non-A, non-B hepatitis (NANBH) has been considered to be the commonest cause of acute sporadic viral hepatitis in India. Serological studies (Macro ELISA) were conducted on 477 such patients from 9 hospitals of Delhi for markers of hepatitis A and acute hepatitis B (Anti-HAV-IgM,HBsAg and anti-HBc-IgM) and 49.7% of these were found to be due to NANBH. On further testing of NANBH sera it was found that both hepatitis C and hepatitis E contribute significantly to acute sporadic jaundice in Delhi, the latter more than the former.

Acute Disease↗
PubMed1998

Serological diagnosis of jaundice epidemics in India.

Enterically transmitted non-A, nonB- hepatitis (ET-NANBH) is a major public health problem in India, where the endemicity of this disease is high and poor public sanitation coupled with compromised quality of drinking water leads to major and minor outbreaks. Sophisticated technics for characterization of hepatitis E virus (HEV) are not easily available/affordable, resulting in continuation of the diagnosis of NANBH for most epidemics. This study attempts to serologically determine the etiology of epidemics of NANBH in India. Eighteen outbreaks of jaundice occurring in various regions of India over a period of twenty months were selected for this laboratory based study. Representative cases of each outbreak were subjected to detailed serological investigation for immunological markers of viral hepatitis. Each serum sample was tested for the immunological markers of acute or recent infection with hepatitis A or B viruses (anti-HAV-IgM, HBsAg and anti-HBc-IgM) by Macro ELISA (Abbott). The sera found to be negative for these three markers ie non-A, non-B hepatitis (NANBH) sera were further tested for anti-HEV by Macro ELISA (anti-HEV EIA, Abbott). A highly significant number of NANBH sera were reactive for anti-HEV in case of almost all the outbreaks. The lowest figure for anti-HEV positivity in NANBH sera of outbreak was compared with anti-HEV positivity in the controls and found to be significantly high. It was concluded that anti-HEV is an important marker revealing probability of the NANBH outbreak being due to HEV.

Biomarkers↗
PubMed1998

Metabolism and excretion of a new anxiolytic drug candidate, CP-93, 393, in healthy male volunteers.

CP-93,393 [(7S,9aS)-1-(2-pyrimidin-2-yloctahydropyrido[1,2-a] pyrazin-7-ylmethyl)pyrrolidine-2,5-dione] is a new anxiolytic drug with highly selective serotonin 5-hydroxytryptamine 1A autoreceptor agonist, alpha2-adrenergic antagonist, and dopamine D2 agonist properties. The excretion, biotransformation, and pharmacokinetics of CP-93,393 were investigated in six healthy male volunteers after oral administration of a 5-mg dose of [14C]CP-93,393. The administered radioactivity was excreted predominantly in the urine. One week after administration of the dose, cumulative excretion amounted to 67.8 +/- 2.5% in the urine and 22.0 +/- 5.6% in the feces. In total, 89.8 +/- 5.7% of the radioactive dose was recovered in urine and feces. Mean maximum plasma concentration values for unchanged CP-93,393 were 10.92 and 1.02 ng/ml for poor metabolizers (PMs) and extensive metabolizers (EMs) of dextromethorphan, respectively. AUC0-infinity values for unchanged CP-93,393 were also greater for PMs than for EMs, whereas the mean maximum plasma concentration and AUC0-infinity values for total radioactivity were similar for the two phenotypes. Less than 0.5% of the dose was excreted in urine as unchanged drug for both EMs and PMs, suggesting extensive metabolism of CP-93,393 in both phenotypes. Hydroxylation at the 5-position of the pyrimidine ring was identified as the main metabolic pathway. 5-Hydroxy-CP-93,393 (M-15) and its glucuronide and sulfate conjugates (M-7 and M-13, respectively) accounted for approximately 51% of the administered dose in excreta of both PMs and EMs. Hydrolysis of the succinimide ring, in combination with 5-hydroxylation and/or conjugation or not, accounted for approximately 9% of the dose. A novel metabolite, apparently resulting from oxidative degradation of the pyrimidine ring, was characterized as the amidine analog M-18. M-15 (47-62%), its sulfate conjugate (M-13, approximately 9%), and the pyrimidine ring-cleaved product (M-18, 7-13%) were identified as the major circulating metabolites for both EMs and PMs. Therefore, CP-93,393 undergoes metabolism by three primary pathways, i.e. 1) aromatic hydroxylation followed by conjugation with glucuronic acid and sulfuric acid, 2) oxidative degradation of the pyrimidine ring, and 3) hydrolysis of the succinimide ring. The identified metabolites accounted for approximately 90, 91, and 92% of the total radioactivity present in urine, plasma, and feces, respectively. The major in vivo oxidative metabolites were also observed after in vitro incubations with human liver microsomes.

Administration, Oral↗
PubMed1998

Acute sporadic viral hepatitis in urban population of a tribal district in Madhya Pradesh.

OBJECTIVE: To estimate the incidence of acute sporadic viral hepatitis and describe its epidemiology in an urban population. DESIGN: A retrospective community survey for jaundice cases. SETTING: Headquarter town of a tribal district, Bastar, in Madhya Pradesh state, India. METHOD: Trained paramedics surveyed about 51,643 population to detect cases of jaundice which occurred in the past one year. Cases were examined to collect clinical and epidemiological data. blood samples were drawn from all cases who had jaundice in the past 3 months for testing them for markers of viral hepatitis. RESULTS: Study estimated the annual incidence of jaundice cases as 244 (95% CI 201-287) per 100,000 population. Almost 95% jaundice cases occurred in summer and monsoon months. People from all socio-economic strata were affected. The incidence of jaundice was found to be the highest in children below 15 years of age (3.7 per 1000) which declined significantly with the increase in age (p = 0.0000). The overall incidence in two sexes was not different statistically (p = 0.7). Of 57 cases who had jaundice in the past 3 months, 19 (33%) were confirmed as having viral hepatitis. Hepatitis A and E combined together contributed 68% (13/19) of acute sporadic cases of viral hepatitis, whereas hepatitis B, C and D accounted for the remaining 32% of the cases. CONCLUSION: The study found the annual incidence of laboratory supported cases of viral hepatitis to be 81 (95 CI 57-106) per 100,000 population, which suggests that it is an important public health problem in India. Hepatitis A was much more prevalent than hepatitis E. Etiology of almost two-thirds of jaundice cases could not be established which require further community studies.

Acute Disease↗
PubMed1998

Prevalence of North India of hepatitis B carrier state amongst pregnant women.

The study was undertaken to determine the hepatitis B carrier rate in North India along with the relative infectivity of the carriers. A total of 1,112 pregnant women were investigated for hepatitis B carrier state during their routine visits to antenatal clinics. All three tiers of the health care delivery system were included from four regions of North India. The sera were screened for the presence of hepatitis B surface antigen (HBsAg), hepatitis B "e" antigen (HBeAg), and antibody to hepatitis B "e" antigen (Anti-HBe) by third generation Macro ELISA tests. The average hepatitis B surface antigen carrier rate was 9.5%. The carriers were found to be of relatively low infectivity with HBeAg and Anti-HBe present in 12.0% and 25.3% of the HBsAg carriers respectively, and both these markers absent in 62.7%. It was concluded that in the past decade the hepatitis B endemicity in North India has probably increased, but the relative infectivity of the carriers remains the same.

Carrier State↗
PubMed1997

Determination of the substance P receptor antagonist CP-122,721 in plasma by narrow-bore high-performance liquid chromatography-ionspray tandem mass spectrometry.

A simple, highly sensitive and specific LC-MS-MS assay was developed for the determination of CP-122,721 (I) in rat and human plasma. I and a structural analog, CP-129,943 (II, internal standard), were extracted from plasma with methyl tert.-butyl ether (MTBE). The dried MTBE extracts were reconstituted and analyzed using a narrow-bore (2.1 mm I.D.) YMC basic HPLC column and a mobile phase of acetonitrile-20 mM ammonium acetate, pH 5 (50:50, v/v). Column effluents were monitored by ionspray tandem mass spectrometry. Multiple reaction monitoring (MRM) using the parent to product ion combinations of m/z 381-->205 and 395-->219 was used to quantitate I and II, respectively. The assay exhibited a linear dynamic range of 0.2-100 ng/ml. Absolute recoveries from plasma were above 80% for both I and II. The precision and accuracy values for the method were within +/-3 and +/-9%, respectively. Sample analysis times were less than 5 min from one injection to the next. The assay has proved to be applicable to the pharmacokinetic study of I in rats.

Animals↗
PubMed1997

Sexually-transmitted disease (STD) markers in multitransfused children in relation to human immunodeficiency virus type-1 (HIV-1) infection: impact of STD markers in blood donors.

Association of serological markers for various sexually transmitted diseases (STDs) with Human Immunodeficiency Virus type 1 (HIV-1) infection among heterosexually promiscuous blood donors is well recognized. However, possibility of similar association among children receiving transfusion from these donors has not been adequately explored. Study on the association of some STD markers with HIV-1 infection in multitransfused (MT) children showed that both HIV-1 positive and HIV-1 negative groups of children had significantly higher prevalence of hepatitis B virus (HBV) markers, i.e. HBsAg (23 and 30 per cent), anti-HBs (46 and 57 per cent), anti-HBc (18 and 23 per cent), antibodies to cytomegalovirus of IgM class (36 and 37 per cent) and IgG class (72.7 and 70 per cent), IgG antibodies to Herpes Simplex Virus type-2 (23 and 23 per cent) compared to control group. However, seropositivity for HIV-1 infection could not be attributed as a risk factor for any of these markers in the group of MT children. On the contrary, significant association of anti HBc, anti HCV, CMV IgG and antitreponemal antibody with HIV-1 infection could be recorded in the group of blood donors. It appeared that due to low prevalence of HIV-1 infection among blood donors in India, both HIV-1 positive and HIV-1 negative groups of MT children received transfusion from HIV negative donors predominantly resulting in a comparable prevalence of STD markers in both the groups of MT children due to cumulative effect of transfusion from HIV-1 negative donors.

Biomarkers↗
PubMed1997

Metabolism and excretion of the novel antipsychotic drug ziprasidone in rats after oral administration of a mixture of 14C- and 3H-labeled ziprasidone.

The metabolism and excretion of ziprasidone (5-[2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-yl]ethyl]-6-++ +chloroindolin-2-one hydrochloride hydrate) were studied in Long Evans rats after oral administration of a single dose of a mixture of 14C- and 3H-labeled ziprasidone. The radioactive dose was quantitatively recovered over 7 days in both male and female rats. The percentage of the dose excreted in urine, bile, and feces of rats was 21.6, 19.2, and 55.6%, respectively. The total excretion in urine and bile suggested that at least 41% of the drug was absorbed. Absorption of ziprasidone was rapid, and the mean plasma concentrations of the unchanged drug and metabolites were slightly higher in the female rats than in the males. The maximal plasma concentrations for ziprasidone and metabolites were reached at 1 hr in both male and female rats. Based on AUC (0-12 hr) values, approximately 59 and 52% of the circulating radioactivity (average of 14C and 3H) was attributable to metabolites in male and female rats, respectively. Ziprasidone was extensively metabolized in rats, and only a small amount of ziprasidone was excreted as unchanged drug. Twelve metabolites were identified by ion spray LC/MS, using a combination of parent ion and product ion scanning techniques. The structures of eight metabolites were unambiguously confirmed by coelution on HPLC with synthetic standards, and four additional metabolites were partially identified. There was a gender-related difference in the excretion of urinary metabolites in Long Evans rats. The major route of metabolism in male rats involved N-dealkylation. In female rats the major metabolites were due to oxidation at the benzisothiazole ring. Based on the structures of these metabolites, four major and two minor routes of metabolism of ziprasidone were identified. The major routes included 1) N-dealkylation of the ethyl side chain attached to the piperazinyl nitrogen, 2) oxidation at the sulfur, resulting in the formation of sulfoxide and sulfone, 3) oxidation on the benzisothiazole moiety (other than sulfur), and 4) hydration of the C==N bond and subsequent oxidation at the sulfur of the benzisothiazole moiety. The minor routes involved N-oxidation on the piperazine ring and hydrolysis of the oxindole moiety.

Administration, Oral↗
PubMed1997

Metabolism and excretion of a new antipsychotic drug, ziprasidone, in humans.

The pharmacokinetics, metabolism, and excretion of a new antipsychotic drug, ziprasidone, were studied in four normal male volunteers after oral administration of a single 20 mg dose of a mixture of 14C- and 3H-labeled ziprasidone. Blood, urine, and feces were collected at various intervals for determination of total radioactivity and metabolic profiles. Eleven days after the dose, 20.3 +/- 1% of the administered radioactivity was recovered in the urine and 66.3 +/- 4.8% in feces. The absorption of ziprasidone was rapid, and the C(max) for ziprasidone and metabolites occurred at 2 to 6 hr postdose. Mean peak serum concentration of unchanged drug was 45 ng/ml and a mean AUC(0-t) of 335.7 ng x hr/ml. Mean peak serum concentration of total radioactivity (average of 3H and 14C) was 91 ng-eq/ml and a mean AUC(0-t) of 724.6 ng-eq x hr/ml. On the basis of AUC(0-t) values, approximately 46% of circulating radioactivity was attributable to unchanged drug. Ziprasidone was extensively metabolized and only a small amount (<5% of the administered dose) was excreted in urine and feces as unchanged drug. Twelve metabolites in human urine and serum were identified by ion-spray LC/MS and LC/MS/MS with simultaneous monitoring of radioactivity. The major urinary metabolites were identified as oxindole-acetic acid and its glucuronide conjugate, benzisothiazole-3-yl-piperazine (BITP), BITP-sulfoxide, BITP-sulfone and its lactam, ziprasidone-sulfoxide, and sulfone similar to those identified in rats. In addition, two novel metabolic pathways (reductive cleavage and N-dearylation of the benzisothiazole ring) were identified for ziprasidone in humans. The metabolites resulted by these pathways were characterized as S-methyl-dihydroziprasidone, S-methyl-dihydro-ziprasidone sulfoxide, and 6-chloro-5-(2-piperazin-1-yl-ethyl)-1,3-dihydro-indol-2-one, respectively. Ziprasidone sulfoxide and sulfone were the major metabolites in human serum. The affinities of the sulfoxide and sulfone metabolites for 5-HT2 and D2 receptors are low with respect to ziprasidone, and are thus unlikely to contribute to its antipsychotic effects. Structures of the major metabolites were confirmed by chromatographic and spectroscopic comparisons to synthetic standards. Based on the structures of these metabolites, four routes of metabolism of ziprasidone were identified: 1) N-dealkylation of the ethyl side chain attached to the piperazinyl nitrogen, 2) oxidation at sulfur resulting in the formation of sulfoxide and sulfone, 3) reductive cleavage of the benzisothiazole moiety, and 4) hydration of the C=N bond and subsequent sulfer oxidation or N-dearylation of the benzisothiazole moiety. The identified metabolites accounted for >90% of total radioactivity recovered in urine.

Adult↗
PubMed1997

Characterization of the novel benzisothiazole ring-cleaved products of the antipsychotic drug ziprasidone.

Characterization of two novel benzisothiazole ring cleaved metabolites of the antipsychotic drug, ziprasidone (ZIP), in rat has been described. Metabolites designated M6 and M9 were isolated from urine and bile of the rat dosed with radiolabeled ZIP and purified by reversed phase HPLC. The chemical structures of these metabolites were assigned based on tandem mass spectrometry in combination with chemical derivatization techniques. M6 and M9 were unaffected upon treatment with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide. Reaction of M9 with aqueous TiCl3 also did not change the HPLC retention time or the CID spectrum of metabolite M9. These data excluded the possibility that these metabolites were owing to N-oxidation and/or aromatic hydroxylation. M6 and M9 were generated only when in vitro incubations of ZIP were conducted with human liver S-9 fraction in the presence of S-adenosyl-L-methionine. Based on these data, metabolites M6 and M9 were identified as S-methyl-dihydro-ZIP and S-methyl-dihylro-ZIP-sulfoxide, respectively. The structure of M9 was unambiguously confirmed by comparing the LC/MS retention time and mass spectral data with synthetic standard. A mechanism for the formation of these metabolites from ZIP is proposed.

Animals↗
PubMed1997

Metabolism and excretion of a novel antianxiety drug candidate, CP-93,393, in Long Evans rats. Differentiation of regioisomeric glucuronides by LC/MS/MS.

The absorption and metabolism of a novel antianxiety drug candidate, CP-93,393, ((7S, 9aS)-2-(pyrimidin-2-yl)-7-(succinimidomethyl)-octahydro-1H-p yrido[1, 2-a]pyrazine) were investigated in bile-cannulated Long Evans rats after oral administration of a single 30 mg/kg base equivalent dose of 14C-CP-93,393 (HCl salt). Urine, bile, plasma, and feces were collected and assayed for total radioactivity. Plasma samples were also analyzed for unchanged drug using an LC/MS/MS assay. Metabolic profiles of 14C-CP-93,393 were obtained in urine, bile, and plasma. Structural characterization of metabolites was carried out by LC/MS using a combination of full scan, product ion, constant neutral loss, and multiple reaction ion monitoring techniques. CP-93,393 was completely absorbed, as less than 1% of the administered radioactivity was recovered in the feces. The major portion of the radioactivity was recovered in bile, suggesting that the biliary route was the primary route of excretion. Total recovery of administered dose was 97.4 +/- 3.3% from male rats and 85.3 +/- 9.6% from female rats. Approximately 32% of the administered radioactive dose was recovered in urine of female rats, while only 20% was recovered in urine of male rats. In contrast, biliary recoveries of the radioactivity were higher for male rats (approximately 77% for males and 53% for females). Mean Cmax values for the unchanged CP-93, 393 and total radioactivity were significantly higher in the female rats than in the male rats. Similarly, mean AUC(0-t) values for the unchanged drug and radioactivity were also higher in female rats. These findings suggested that CP-93,393 was eliminated more rapidly in the male rats than in the female rats. CP-93,393 and a total of 16 metabolites were identified in urine, bile, and plasma. Based on the structures of oxidative metabolites, four metabolic pathways of CP-93,393 were identified: hydroxylation at the pyrimidine ring, hydroxylation at the succinimide ring, hydroxylation alpha to the nitrogen of the piperazine ring, and hydrolysis of amide bond of the succinimide ring. The major oxidative metabolites were excreted as sulfate and/or glucuronide conjugates. The structures of regioisomeric glucuronides were established by a novel tandem mass spectrometric technique. The glucuronides were dissociated at the orifice, and the resulting aglycones were then analyzed by MS/MS studies. The identified metabolites accounted for >90% of the total radioactivity present in urine, bile, and plasma.

Animals↗
PubMed1997

Metabolism and excretion of a new antianxiety drug candidate, CP-93,393, in cynomolgus monkeys: identification of the novel pyrimidine ring cleaved metabolites.

The metabolism and excretion of a new anxiolytic/antidepressant drug candidate, CP-93,393, ((7S, 9aS)-1-(2-pyrimidin-2-yl-octahydro-pyrido[1, 2-a]-pyrazin-7-yl-methyl)-pyrrolidine-2,5-dione) were investigated in cynomolgus monkeys after oral administration of a single 5 mg/kg dose of 14C-CP-93,393. Urine, bile, feces, and blood samples were collected and assayed for total radioactivity, parent drug, and metabolites. Total recovery of the administered dose after 6 days was 80% with the majority recovered during the first 48 hr. An average of 69% of the total radioactivity was recovered in urine, 4% in bile, and 7% in feces. Mean Cmax and AUC(0-infinity) values for the unchanged CP-93,393 were 143.2 ng/ml and 497.7 ng.hr/ml, respectively, in the male monkeys and 17.2 ng/ml and 13.7 ng.hr/ml, respectively, in the female monkeys. HPLC analysis of urine, bile, feces, and plasma from both male and female monkeys indicated extensive metabolism of CP-93,393 to several metabolites. The identification of metabolites was achieved by chemical derivatization, beta-glucuronidase/sulfatase treatment, and by LC/MS/MS, and the quantity of each metabolite was determined by radioactivity detector. CP-93,393 undergoes metabolism by three primary pathways, aromatic hydroxylation, oxidative degradation of the pyrimidine ring, and hydrolysis of the succinimide ring followed by a variety of secondary pathways, such as oxidation, methylation, and conjugation with glucuronic acid and sulfuric acid. The major metabolites, oxidation on the pyrimidine ring to form 5-OH-CP-93,393 (M15) followed by glucuronide and sulfate conjugation (M7 and M13), accounted for 35-45% of the dose in excreta. Two metabolites (M25 and M26) were formed by further oxidation of M15 followed by methylation of the resulting catechol intermediate presumably by catechol-O-methyl transferase. A novel metabolic pathway, resulting in the cleavage of the pyrimidine ring, was also identified. The metabolites (M18, M20, and M21) observed from this pathway accounted for 8-15% of the dose. Aliphatic hydroxylation of the succinimide ring was a very minor pathway in monkey. 5-Hydroxy-CP-93,393 (M15, 37-49%), its sulfate and glucuronide conjugates (M7 and M13, approximately 34%), and the pyrimidine ring cleaved product (M18, approximately 8%) were the major metabolites in monkey plasma. The identified metabolites accounted for approximately 90, 93, 97, and 92% of the total radioactivity present in urine, bile, plasma, and feces, respectively. The major in vivo oxidative metabolites were also observed after in vitro incubations with monkey liver microsomes.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1997

Epidemiology of endemic viral hepatitis in an urban area of India: a retrospective community study in Alwar.

In a community study during a reference period of 1 year, 192 cases of jaundice were detected in an urban population of 69,440 in Alwar, Rajasthan. Detected by paramedics and confirmed by physicians, these cases gave an annual incidence of 2.76 (95% CI: 2.37-3.15) per 1000 population. At least one of these patients died, giving a case fatality ratio of 0.6%. The jaundice cases occurred in all areas investigated, and affected all socioeconomic strata. About 94% of the affected families had only single cases. Although cases occurred throughout the year, more than 59% occurred during June-September, which are the summer and monsoon months. The incidence was highest (5.23 per 1000) among under-5-year-olds and declined progressively and significantly thereafter. Males had a higher incidence than females at all ages; the differences were not significant. Blood samples from 56 cases who had jaundice in the last 3 months of the reference period were tested for markers of viral hepatitis. Of these, 18 (32.1%), 1 (1.8%), 0, 2 (3.6%), and 4 (7.1%) were found to have hepatitis A, B, C, D and E, respectively. The etiology of the remaining 31 cases (55%) could not be established; previously, they would have been included in the NANB (non-A, non-B) category, inflating its proportion. Hepatitis A (HA) was the predominant type; being comparatively mild, it is perhaps underrepresented in hospital-based data. Many HA cases were in adults, which may be the beginning of an age shift of HA to the right owing to improvements in living standards of the study population. Five cases were carriers of hepatitis B virus (HBV), indicating the importance of HBV infection in India as well. Finally, the study found the annual incidence of laboratory-supported cases of viral hepatitis to be 1.24 (95% CI: 0.98-1.5) per 1000 population, which suggests that it is a major public health problem in India.

Adolescent↗