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J Costa

Publications and source records attributed to J Costa.

At least 145 records · Page 8Linked to original sources
PubMed1996

Variation of cytokine patterns related to therapeutic response in diffuse cutaneous leishmaniasis.

Diffuse cutaneous leishmaniasis is a rare entity characterized by disseminated cutaneous nodules associated with specific anergy to leishmanial antigens. A low but not absent IFN-gamma expression by cells present in cutaneous lesions has been documented during the active phase of diffuse cutaneous leishmaniasis. In this study we confirm this observation, and extend it by showing a similar pattern in peripheral blood mononuclear cells and the variation of mRNA cytokine expression pattern during different stages of the disease. During active disease, patients did not express mRNA for IFN-gamma, while expressing mRNA for IL-2, IL-4, and IL-10. In contrast, an expression of IFN-gamma and low IL-10 was observed after treatment-induced transient healing of cutaneous lesions. In three patients we have been able to analyze a third PBMC sample obtained after clinical relapse, documenting in all of them decreased IFN-gamma expression with no expression of IL-10. Although there was an association between the appearance of IFN-gamma expression and clinical improvement, with marked expression of IFN-gamma mRNA and decreased expression of mRNA for IL-10 after treatment, this was not sufficient to prevent relapse in these patients. Therefore, it is possible that factors other than the cytokines characteristic of the Th1 and Th2 balance are implicated in the inability of diffuse cutaneous leishmaniasis patients to mount an anti-Leishmania immune response causing clinical improvement.

Adolescent↗
PubMed1996

Characterisation of a developmentally related polypeptide with glutelin solubility characteristics from Lupinus albus L.

Proteins from Lupinus albus L. cv. Rio Maior seeds were fractionated according to solubility criteria. Patterns of concanavalin A (ConA)-binding polypeptides from the different classes, albumins, globulins, glutelins and prolamins, were established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two bands of apparent molecular masses of 29 and 23.5 kDa with glutelin solubility characteristics bound the lectin. The 23.5-kDa band was separated by two-dimensional electrophoresis into two components: one glycosylated and heterogeneous with an isoelectric point of approx. 10 (designated as G23) and another, not detected with ConA, precipitating in the first dimension. The amino acid and hexosamine analysis of G23 showed that it is particularly rich in Gly (11.2%), Glx (10.0%), Ser (9.0%), Leu (8.2%), Asx (7.5%), and Pro (6.7%) and that it has a considerable content of the sulphur-containing amino acids Met (2.0%) and Cys (5.8%) and contains glucosamine. The determined N-terminal amino acid sequence of G23 was: 1KG(R)V5KGTGD10(T)PXXV15XLY(N)R20T, and this had no significant similarity to any of the amino acid sequences contained in the data bank SWISS-PROT 26. The glycoprotein G23 was completely deglycosylated with peptide-N-glycosidase F, yielding a homogeneous 21-kDa polypeptide composed of approximately 191 amino acids. The structures of the major N-linked neutral oligosaccharides of G23, determined by exoglycosidase sequencing, were as follows: Man alpha 2Man alpha 6(Man alpha 3) Man alpha 6(Man alpha 2Man alpha 2Man alpha 3)Man beta 4GlcNAc beta 4 GlcNAc (13%); +/- Man alpha 2Man alpha 6(Man alpha 3)Man alpha 6(+/- Man alpha 2 Man alpha 2 Man alpha 3)Man beta 4GlcNAc beta 4GlcNAc (29%); Man alpha 6(Man alpha 3) Man alpha 6(Man alpha 2Man alpha 3)Man beta 4GlcNAc beta 4GlcNAc (13%); Man alpha 6(Man alpha 3)Man alpha 6(Man alpha 3)Man beta 4GlcNAc beta 4GlcNAc (16%); Man alpha 6(Man alpha 3)(Xyl beta 2)Man beta 4GlcNAc beta 4GlcNAc (28%). Changes in G23 abundance during seed development, germination and seedling growth were monitored with a specific antibody. The glycoprotein G23 started to accumulate appreciably during seed formation between the 40th and the 50th days after anthesis and was detected following seed imbibition, until the 9th day in cotyledons, the 2nd day in roots and the 4th day in hypocotyls and leaves.

Amino Acid Sequence↗
PubMed1996

Angiotropic large cell lymphoma presenting as primary adrenal insufficiency.

Angiotropic large cell lymphoma is reported in two patients who developed severe metabolic acidosis and unexplained hypotension before death. In addition to the usual multiorgan involvement of the disease, the adrenal glands of both patients were symmetrically enlarged. Histologically, the cortical vessels were engorged and filled with neoplastic lymphoid cells of B-cell lineage, whereas the parenchymal cells were compressed and atrophic. Angiotrophic large cell lymphoma seems to be a distinct and unrecognized cause of primary adrenal insufficiency, and should be included in the differential diagnosis of adrenal hormone deficiency.

Adrenal Glands↗
PubMed1996

Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded by rapid clearance of HCV-RNA from serum.

BACKGROUND/AIMS: Prediction of response to interferon therapy is important in the management of chronic hepatitis C. Pre-therapy data are valuable but they may be inaccurate in some cases. Our aim was to investigate whether the biochemical and virological events that occur early during interferon therapy in chronic hepatitis C may predict the final result of the treatment. METHODS: ALT and serum HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a standard 6-month course of interferon therapy. Eleven patients with a sustained response, 23 who responded but subsequently relapsed and 19 who did not respond were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV). RESULTS: After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained responders, in 26% of transient responders (p = 0.02) and in none of the non-responders. Corresponding figures after 8 weeks of therapy were 82% in sustained responders, 61% in transient responders and 9% in non-responders. The difference between sustained and transient responders at this time was not significant. After 4 weeks of therapy, 82% of sustained responders, 52% of transient responders and none of the non-responders presented normalization of alanine transferase. The difference between sustained and transient responders was not significant. Corresponding figures for normalization of alanine transferase at 8 weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained responders, 70% of transient responders and none of the non-responders had cleared HCV-RNA from serum. CONCLUSIONS: A rapid normalization of alanine transferase induced by interferon therapy is associated with response, but does not differentiate between transient and permanent response. In contrast, clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is significatively associated with sustained response. Testing for HCV-RNA early during interferon administration may be valuable for further decisions concerning therapy in patients with chronic hepatitis C.

Adult↗
PubMed1996

Nimodipine fails to enhance the analgesic effect of slow release morphine in the early phases of cancer pain treatment.

We assessed nimodipine's ability to increase the analgesic effect of morphine in 32 patients suffering from cancer pain in a double-blind, placebo controlled cross-over study. Morphine administration began a few days before the start of the study. The analgesic effects of two combinations were compared: morphine (M) plus placebo (P) and morphine plus 90 mg/24 h of nimodipine (N). The study lasted 8 days, including the wash-out period, and the following sequence of treatments was applied: M + P or M + N on days 1, 2 and 3; only M on days 4 and 5; and M + N or M + P on days 6, 7 and 8. Morphine dose was individualised according to the intensity of the patient's pain and the same dose was maintained throughout the study period. Analgesic response was evaluated using four 10 cm visual analogue scales of quantitative variables for pain intensity, pain relief, sleep quality and mood. A verbal rating of qualitative variables was also scored following validated descriptors of pain in the Spanish language. No significant statistical differences were found in analgesic effect between combined treatment with nimodipine or placebo, as measured on any of the scales. In order to take into account both the short duration of treatment (8 days), and nimodipine's pharmacokinetic characteristics (half-life of 6 h and steady state of 36 h), we compared treatment with nimodipine or placebo on the third day of use, at which time, likewise, there were no statistically significant differences on any of the scales. However, when the same statistical tests were used for comparison of results with pre-treatment baseline values, highly significant differences between mean scores on the scales for pain relief and pain intensity were found. Based on these negative results we conclude that nimodipine given orally at a dose of 30 mg every 8 h does not enhance analgesia when associated with morphine in the early phases of treatment for cancer pain. Our study also gives clear evidence of a placebo effect.

Administration, Oral↗
PubMed1996

Highly sensitive nonradioactive single-strand conformational polymorphism. Detection of Ki-ras mutations.

Mutation detection by single-strand conformational polymorphism (SSCP) analysis is more difficult when the variant is limited to a small proportion of target sequences in a sample. Use of SYBR-Green II, a sensitive, nonradioactive, minimally hazardous nucleic acid stain, permits detection of Ki-ras mutants present as less than 0.5% of the target sequences. The polymerase chain reaction (PCR) primers we have selected produce an amplicon that distinguishes all clinically observed variants in Ki-ras codons 12 and 13 from the wild type. We compared mutant discrimination and SYBR-Green II detection sensitivity in three formats: (a) standard MDE gel SSCP, (b) rapid minigel MDE using an internal gel temperature controller, and (c) rapid resolution in chilled 15% (37.5:1) acrylamide minigels. All these gels are easily evaluated by standard ultraviolet transillumination and digital image analysis. This ssDNA staining method is rapid, highly reproducible, and minimally hazardous, and minigels use 25% the reagents of most other systems. Our improvements are relevant for the detection of mutations in pathologic samples with minimal targets, such as fine-needle aspirates, and body fluids in which mutated alleles of a gene may be present at low levels but carry a high level of diagnostic or prognostic importance.

DNA↗
PubMed1996

Ex vivo antibacterial properties of rufloxacin compared with those of norfloxacin in a study with healthy volunteers.

Twelve adult males participated in a randomized crossover phase I clinical trial comparing serum bactericidal titers (SBTs), urine bactericidal titers (UBTs), and urine killing rates (UKRs) against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, after the administration of single 400-mg doses of rufloxacin and norfloxacin at different times up to 72 h postdose. SBTs were significantly higher (P < 0.05) against E. coli from 8 to 48 h and against S. aureus from 4 to 24 h with rufloxacin. UBTs for E. coli were higher (P < 0.05) for norfloxacin at early sample times (0 to 8 h) but higher for rufloxacin (P < 0.05) at sample times from 16 h on for both E. coli and S. aureus. Similar UKRs were obtained for both quinolones for 0 to 2 h and 8 to 12 h, but the UKR was maintained for 72 h with rufloxacin. The high and sustained mean levels of rufloxacin in urine (> 35 micrograms/ml), median UBTs (> 32 for E. coli and 16 for S. aureus) and UKRs for E. coli suggest prolonged urine antibacterial activity (for at least 72 h) and its use as a single 400-mg dose in the treatment of uncomplicated cystitis.

Adult↗
PubMed1996

Comparative study of three methods for genotyping hepatitis C virus strains in samples from Spanish patients.

Hepatitis C virus (HCV) genotypes may be investigated by a variety of laboratory methods that target different parts of the HCV genome and have various degrees of technical difficulty. Since the choice of a particular method is difficult, we compared the performance of (i) a type-specific PCR with type-specific primers from the core region, (ii) molecular hybridization of the PCR-amplified 5' noncoding region to type-specific probes, and (iii) identification of type-specific antibodies against epitopes of nonstructural region 4 by enzyme-linked immunosorbent assay (ELISA). One hundred fifty-one patients with biopsy-proved chronic hepatitis and HCV RNA in serum were investigated. The HCV genotype was identified in 99%, 100%, and 85% of the cases by type-specific PCR, probe hybridization, and ELISA, respectively. The type-specific PCR disclosed infection with type 1a in 3%, type 1b in 74%, and type 3a in 4% of the cases and suggested infection with two or more HCV types, including 2a/2c and 2b, in the remaining 18%. Apparently mixed infections were more prevalent in patients with past intravenous drug use (P < 0.001), but cloning and sequencing of PCR products did not confirm a mixed infection in any of the four cases investigated. Concordant results were obtained by the three procedures with virtually all of the samples in which the type-specific PCR revealed a single HCV genotype. Type-specific hybridization and ELISA usually recognized the genotype producing the strongest DNA band in samples in which type-specific PCR suggested a mixed infection. In conclusion, the three procedures evaluated in this study are reliable for investigation of HCV genotype. Type-specific PCR provides information about HCV subtypes, but a mixed infection detected with this method should be interpreted with caution.

Enzyme-Linked Immunosorbent Assay↗
PubMed1996

Low dose alpha interferon therapy can be effective in chronic active hepatitis C. Results of a multicentre, randomised trial.

BACKGROUND: There is some controversy concerning the efficacy of low dose alpha interferon therapy in chronic hepatitis C. AIMS: To evaluate the effectiveness of treatment with low doses of alpha interferon in chronic hepatitis C. PATIENTS: One hundred and forty one patients with anti-HCV positive chronic active hepatitis C from six hospitals were enrolled in the study. METHODS: Patients were randomised to treatment with 5 MU (group A) or 1.5 MU (group B) injections. The dose was reduced in responders from group A or increased in non-responders from group B to maintain treatment with the minimal effective dose. Patients were treated for 48 weeks and followed up for 24 additional weeks with no treatment. Normalisation of alanine aminotransferase (ALT) was used to evaluate response. RESULTS: A sustained response was seen in eight patients from group A (12%) and in 15 (21%) from group B. This difference was not statistically significant. Increasing the dose of interferon led to sustained response in only five of 58 patients (9%) from group B who did not respond to 1.5 MU injections. In contrast, 15 of 21 patients (71%) in whom ALT remained normal with 1.5 MU injections developed a sustained response. By multivariate analysis sustained response seemed associated with young age and was more frequent in patients with genotype 3 HCV infection. Sustained response was preceded by a rapid normalisation of ALT and was inversely related to the amount of alpha interferon necessary to maintain ALT at low values during treatment. CONCLUSIONS: Some patients with chronic hepatitis C are very sensitive to alpha interferon and can be successfully treated with low doses. Treatment with higher doses may be effective in a minority of patients who do not respond to low doses.

Alanine Transaminase↗
PubMed1996

Pharmacological properties of hirudin and its derivatives. Potential clinical advantages over heparin.

Hirudin and its derivatives represent the first parenteral anticoagulants introduced since the discovery of heparin in the early 1900s. Hirudin, the naturally occurring anticoagulant of the leech, is a single peptide chain of 65 amino acids with a molecular weight of about 7000. Recombinant technology has developed methods to produce recombinant forms of hirudin (r-hirudin) in sufficient quantities for therapeutic use. Hirudin is a potent thrombin-specific inhibitor that forms equimolar complexes with thrombin. It represents a new anticoagulant agent in a field in which heparin has been the only available drug for many years. In contrast to heparin, hirudin does not require antithrombin III as a cofactor, is not inactivated by antiheparin proteins, has no direct effects on platelets and may also inactivate thrombin bound to clot or the subendothelium. In humans, experience with r-hirudin in preventing or treating venous thromboembolism is very preliminary. However, r-hirudin achieved promising results in patients with unstable angina, or following coronary angioplasty. In patients with acute myocardial infarction, 3 important clinical trials were stopped because of an excess of bleeding complications. At present, the discovery of a r-hirudin regimen that is more efficacious than heparin and at least as safe needs a reappraisal of the drug in further trials.

Angina, Unstable↗
PubMed1996

Identification of mutations in the Ki-ras gene in human retinoblastoma.

PURPOSE: To investigate the mutational status of the Ki-ras gene in retinoblastoma and to evaluate a correlation of the genotype with clinical and histopathologic variables. METHODS: Tumor samples were microdissected from sectioned archival paraffin-embedded tissue. Ki-ras genomic sequences (exons 1 and 2) were amplified by polymerase chain reaction then analyzed by single-strand conformation polymorphism and direct sequencing. Tissue sections, flanking the analyzed samples, were stained with hematoxylin and eosin for examination by light microscopy. RESULTS: Four of 12 tumors had mutation in exon 1, codon 12 of the Ki-ras gene; none had mutation in exon 2. Signal intensity of the mutated alleles indicates clonal mutation in the tumor cell populations. One of four bilateral tumors was mutated, and all three samples with undifferentiated histologic appearance harbored a clonal Ki-ras mutation. However, only one of nine moderately to poorly differentiated tumors harbored a mutation. CONCLUSIONS: Ki-ras, an oncogene seldom altered in neuroectodermal neoplasms, is mutated in one third of the retinoblastomas studied. The Ki-ras mutations are clonal, suggesting that affected cells have a selective growth advantage. The mutations are present and are likely to play a pathogenetic role in heritable and sporadic retinoblastomas. These results suggest that mutations in Ki-ras are preferentially associated with undifferentiated tumors.

Adolescent↗
PubMed1995

Comparative genomic hybridization detects novel deletions and amplifications in head and neck squamous cell carcinomas.

To gain a better understanding of genetic changes in squamous cell carcinomas of the head and neck we used comparative genomic hybridization for the analysis of 13 primary tumors. Copy number increases were most frequently observed on chromosomes 3q (10 cases) and 5p (8 cases) and less frequently on 1q (4 cases), 2 (1 case), 7 (2 cases), 8q (2 cases), 9 (1 case), 10p (2 cases), 13q (2 cases), 14q (1 case), 16 (1 case), 17 (2 cases), 20p (2 cases), 21q (1 case) and 22q (1 case). Copy number decreases occurred most frequently at 3p (5 cases), 5q (4 cases), 19p (6 cases), and 19q (5 cases). Copy number decreases also were observed on 1p (2 cases), 2q (2 cases), 4p (2 cases), 4q (2 cases), 7q (2 cases), 8p (1 case), 10q (1 case), 11p (2 cases), 11q (3 cases), 13q (3 cases), 14q (1 case), 16p (1 case), 17p (3 cases), 17q (1 case), 18q (1 case), and 22 (2 cases). Eight sites exhibiting significant sequence amplification were mapped to 3q26-->qter (3 cases), 11q13 (2 cases), 12p (2 cases), 2q33-36 (1 case), 7q21-22 (1 case), 7q33-->qter (1 case), 9p (1 case), and 13q32-->qter (1 case). Our data suggest that the regions 3q26-->qter and 5p may harbor oncogenes important for initiation or progression of squamous cell carcinomas of the head and neck. In addition, comparative genomic hybridization defines a subgroup of tumors with 11q13 involvement, the location of the PRAD1/(CCND1)/cyclin D1 gene.

Adult↗
PubMed1995

Microwave treatment of serum facilitates detection of hepatitis B virus DNA by the polymerase chain reaction. Results of a study in anti-HBe positive chronic hepatitis B.

Investigation by polymerase chain reaction of HBV-DNA in serum from chronic hepatitis B virus carriers is not widely used for routine diagnosis because polymerase chain reaction assays are complex and may be too sensitive. We investigated the sensitivity, the specificity and the possible value for clinical use of a simplified polymerase chain reaction method in which a single, 30 cycles round of polymerase chain reaction is performed using only 10 microliters of serum treated with microwaves. The efficiency of the polymerase chain reaction in amplifying HBV-DNA was greater after microwave irradiation of serum than after alkaline extraction, but lower than after protein digestion and phenol chloroform precipitation. Despite its simplicity and high sensitivity, the assay was very specific. Studies in anti-HBe positive chronic hepatitis B virus carriers demonstrated HBV-DNA sequences in 1/15 (7%) healthy carriers, in 4/20 (20%) patients with slight alanine aminotransferase elevation, in 16/18 (89%) with marked alanine aminotransferase elevation and in all 20 with fluctuating alanine aminotransferase levels. In the latter, HBV-DNA was detected either at exacerbation (two cases), during remission (one case) or both (17 cases). HBV-DNA was detected by classical dot-blot hybridization in only 24/58 (41%) samples that were positive by the simplified polymerase chain reaction method. Although extremely high sensitivity is not achieved, microwave irradiation of serum simplifies considerably the detection of small amounts of HBV-DNA and makes polymerase chain reaction suitable for monitoring patients in whom weak hepatitis B virus replication is associated with ongoing liver disease.

Adult↗
PubMed1995

The incidence of human parvovirus B19 infection during pregnancy and its impact on perinatal outcome.

A prospective study of parvovirus B19 infection during pregnancy was conducted at a large teaching hospital in Barcelona, Spain. Women (1610) who were < 28 weeks pregnant at enrollment were screened for parvovirus infection. The prevalence of IgG positivity was 35.03% (564/1610). The incidence of acute infection during pregnancy was 3.7% (60/1610). There were five abortions among the B19-infected women but only one was caused by parvovirus, as assessed by histologic examination and polymerase chain reaction assay. The incidence of fetal loss caused by parvovirus was, therefore, 1.66% (1/60). The remaining 55 pregnancies were uneventful, and at 1 year of age, none of the infants had serious abnormalities. The incidence of vertical transmission of infection was estimated at 25%. This study provides evidence that although acute parvovirus infection may occur relatively commonly during pregnancy, an adverse fetal outcome is a rare complication.

Adult↗
PubMed1995

A double-blind, placebo-controlled study of a CCK-B receptor antagonist, CI-988, in patients with generalized anxiety disorder.

This multicenter, double-blind, placebo-controlled, parallel-group, randomized study assessed the efficacy, safety, and tolerability of a novel CCK-B antagonist CI-988 in the treatment of generalized anxiety disorder (GAD). Patients received placebo or CI-988 (300 mg/day, thrice daily) for 4 weeks. Patients with a primary diagnosis of GAD according to DSM-III-R criteria were randomized. The study design included a 1- to 2-week single-blind placebo baseline phase, followed by a 4-week double-blind treatment phase. Efficacy was measured weekly by Hamilton Rating Scale for Anxiety (HAM-A), Clinical Global Impressions of Severity and Change, UCLA-Multi Dimensional Anxiety Scale, and Hamilton Rating Scale for Depression. Patients were also evaluated to determine whether they met criteria for irritable bowel syndrome (IBS) at screening and were evaluated with a gastrointestinal visual analog scale at each visit. Eighty-eight patients were randomized to CI-988 (N = 45) and placebo (N = 43) at three centers. CI-988 did not demonstrate an anxiolytic effect superior to placebo in this clinical trial. There was no significant difference in mean change in HAM-A total between placebo (-7.73) and CI-988 (-8.64). However, a significant treatment-by-center interaction and a highly variable placebo response rate among the three centers limit the interpretation of the results. CI-988 did not have an effect on symptoms of IBS other than diarrhea, which worsened in patients with IBS. Other than a higher incidence of some gastrointestinal symptoms (diarrhea, dyspepsia, flatulence, and nausea), CI-988 was well tolerated. Results suggest that testing higher oral doses of CI-988 may be warranted.

Adult↗
PubMed1995

Improved polymerase chain reaction detection of clonal T-cell lymphoid neoplasms.

We have developed and tested a rapid and sensitive method of detecting expansion of T-cell clones using the polymerase chain reaction (PCR) and a single set of consensus primers for the V and J regions to amplify rearranged T-cell receptor-gamma (TCR-gamma) genes. Monoclonality was continued in all of the 18 cases of T-cell neoplasms tested, but not in reactive lymphadenopathy, non-Hodgkin's B lymphomas, and Hodgkin's disease. PCR analysis, using the primer sequence outlined in this study, had an overall specificity of 100% when compared with Southern blot analysis. No false-negative results were observed, certainly owing to the choice of consensus primers and to the control of PCR reactions on agarose gels before testing for clonality by separation of PCR products on polyacrylamide gels. This method for the detection of T-cell monoclonality can be especially useful in cases that are diagnostically problematic with standard histological and immunological analysis and in cases where the material available is limited.

Base Sequence↗
PubMed1995

Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications.

Zolpidem is an imidazopyridine which differs in structure from the benzodiazepines and zopiclone. It is a strong sedative with only minor anxiolytic, myorelaxant and anticonvulsant properties, and has been shown to be effective in inducing and maintaining sleep in adults. The available evidence suggests that zolpidem produces no rebound or withdrawal effects, and patients have experienced good daytime alertness. Zolpidem 10mg in non-elderly and a reduced dose of 5mg in elderly individuals are clinically effective. In humans, the major metabolic routes include oxidation and hydroxylation; none of the metabolites appears to be pharmacologically active. The pharmacological activity of zolpidem results from selective binding to the central benzodiazepine receptors of the omega 1 subtype. Zolpidem is approximately 92% bound to plasma proteins; absolute bio-availability of zolpidem is about 70%. After single 20mg oral doses, typical values of pharmacokinetic variables for zolpidem in humans are: a peak plasma concentration of 192 to 324 micrograms/L occurring 0.75 to 2.6 hours postdose; a terminal elimination half-line of 1.5 to 3.2 hours; and total clearance of 0.24 to 0.27 ml/min/kg. Zolpidem pharmacokinetics are unchanged during multiple-dose treatment. Zolpidem pharmacokinetics are not significantly influenced by gender. Clearance of zolpidem in children is 3 times higher than in young adults, and is lower in very elderly people. There are no significant differences in the pharmacokinetic parameters between various racial groups. Dosage reduction appears to be prudent in patients with renal disease, and caution should be exercised when prescribing zolpidem to elderly patients with hepatic impairment. Coadministration of haloperidol, cimetidine, ranitidine, chlorpromazine, warfarin, digoxin or flumazenil do not alter the pharmacokinetics of zolpidem; flumazenil predictably antagonises the hypnotic effects of zolpidem. Alertness tends to be reduced when cimetidine is combined with zolpidem. Volunteers treated with imipramine plus zolpidem developed anterograde amnesia.

Adult↗