RESUMEN
Pyrenean Mountain Dog (PMD) is an ancient dog breed firstly described in XIV century in the Pyrenees Region and nowadays diffused both in Europe and in the US. Hereditary Cataract (HC), defined as the inherited opacity of the lens, involves clinical signs ranging from reduced vision to glaucoma. A molecular basis of HC was firstly described in Staffordshire Bull Terriers and then reported in multiple canine breeds. The HC-associated variation is a single nucleotide deletion in HSF4 gene that introduces a premature stop codon (c.962del, p.Ala321*). Multifocal Retinopathy 1 (MR) is an ocular disorder characterized by multiple areas of retinal degeneration, caused in various dog breeds (including PMD) by a single nucleotide variant (SNV) in BEST1 gene that generates a premature stop codon (c.73G>A, p.Arg25*). Degenerative Myelopathy (DM) is an adult-onset, progressive neurodegenerative disease and it is associated to a SNV in SOD1 gene causing a change in aminoacidic sequence of the protein (c.118G>A, p.Glu40Lys). This causative variant has been described in various dog breeds, including PMD. Aim of this study was to determine the allele frequencies for the abovementioned three genetic diseases in the Italian breeding PMD population. The survey found no dogs carrying the allele (deletion) associated with HC, while three dogs (6 %) were heterozygous (G/A) for the MR-associated variant, and seven dogs (13 %) were heterozygous (G/A) for the DM-associated alteration, indicating that the variant alleles frequency were 0 %, 3 %, and 7 %, respectively. Appropriate mating management is suggested for the prevention of genetic diseases spreading in the PMD population.
Asunto(s)
Catarata , Enfermedades de los Perros , Enfermedades Neurodegenerativas , Enfermedades de la Retina , Enfermedades de la Médula Espinal , Perros , Animales , Alelos , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/veterinaria , Codón sin Sentido , Genotipo , Enfermedades de la Retina/veterinaria , Enfermedades de la Médula Espinal/veterinaria , Catarata/genética , Catarata/veterinaria , Nucleótidos , Enfermedades de los Perros/genéticaRESUMEN
Patients with cancer have a well-known and higher risk of vaccine-preventable diseases (VPDs). VPDs may cause severe complications in this setting due to immune system impairment, malnutrition and oncological treatments. Despite this evidence, vaccination rates are inadequate. The Italian Association of Medical Oncology [Associazione Italiana di Oncologia Medica (AIOM)] has been involved in vaccination awareness since 2014. Based on a careful review of the available data about the immunogenicity, effectiveness and safety of flu, pneumococcal and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, we report the recommendations of the AIOM about these vaccinations in adult patients with solid tumors. The AIOM recommends comprehensive education on the issue of VPDs. We believe that a multidisciplinary care model may improve the vaccination coverage in immunocompromised patients. Continued surveillance, implementation of preventive practices and future well-designed immunological prospective studies are essential for better management of our patients with cancer.
Asunto(s)
COVID-19 , Vacunas contra la Influenza , Gripe Humana , Neoplasias , Infecciones Neumocócicas , Adulto , Humanos , SARS-CoV-2 , Gripe Humana/complicaciones , Estudios Prospectivos , Estaciones del Año , COVID-19/prevención & control , COVID-19/complicaciones , Neoplasias/complicaciones , Neoplasias/terapia , Vacunación , Infecciones Neumocócicas/complicacionesAsunto(s)
Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Neumonía/complicaciones , Poliendocrinopatías Autoinmunes/complicaciones , Adulto , COVID-19 , Infecciones por Coronavirus/terapia , Cuidados Críticos , Femenino , Predisposición Genética a la Enfermedad , Terapia de Reemplazo de Hormonas , Humanos , Italia , Pandemias , Neumonía/terapia , Neumonía Viral/terapia , Poliendocrinopatías Autoinmunes/tratamiento farmacológico , Poliendocrinopatías Autoinmunes/genética , Respiración ArtificialRESUMEN
OBJECTIVE: Bacterial infections are a leading factor in the progression from compensated to decompensated cirrhosis, with consequent worsening of the prognosis, and concerted efforts have been made to reduce infections and improve the survival rate of these patients. We retrospectively investigated the rate of infections in hospitalized cirrhotic patients under treatment with rifaximin. PATIENTS AND METHODS: We enrolled 649 patients whose clinical and personal data, prescribed therapy, microbiological findings and laboratory tests were collected from previous discharge letters and our institution database. The efficacy of rifaximin in preventing several types infection was evaluated by comparing outcomes for rifaximin-treated patients vs patients receiving no antibiotic treatment. RESULTS: The risk of developing selected bacterial infections was significantly lower in patients treated with rifaximin (OR 0.29; 95% CI 0.20-0.40, p < 0.001). CONCLUSIONS: Continuous treatment with rifaximin may prevent bacterial infections in cirrhotic patients.
Asunto(s)
Antiinfecciosos/uso terapéutico , Infecciones Bacterianas/prevención & control , Cirrosis Hepática/complicaciones , Rifamicinas/uso terapéutico , Infecciones Bacterianas/complicaciones , Humanos , Rifaximina , Resultado del TratamientoRESUMEN
The objective of this study was to determine the genetic structure and variability of Bionda Piemontese and Bianca di Saluzzo (Piedmont, Northwest Italy) using an international set of microsatellite loci (AVIANDIV-FAO). Differences compared with commercial lines and other Italian breeds were verified to justify the implementation of conservation programmes. Flock contribution to genetic variability was assessed following the approach implemented in the MolKin software. Comparison was performed using the fixation index and the Reynolds genetic distance. The most likely number of different populations was estimated using the clustering procedure implemented in STRUCTURE. The molecular information suggests that management practices could have prevented random mating and produced inbreeding and heterogeneity across flocks. In this respect, Bionda and Bianca show substructuring and are more similar to British breeds than other continental European breeds. Bionda and Bianca fit into the European breeds provided with the highest number of alleles and expected heterozygosity. There is a clear distinction between the Piedmont breeds and the other populations. The Piedmont poultry differ from both commercial lines and other Italian breeds and retain a high level of genetic variability. As for other indigenous breeds, Bionda and Bianca could make an original contribution to the industry in the future. A collective planned approach to restoration is essential, because the flocks are managed with poor regulation. Enhancing connection between breeders with an efficient replacement interchange and mating plan is the right way of controlling inbreeding, preventing substructuring and increasing variability within the flocks.
Asunto(s)
Pollos/genética , Variación Genética , Repeticiones de Microsatélite , Animales , Cruzamiento , Pollos/clasificación , Femenino , Italia , Filogenia , Análisis de Secuencia de ADNRESUMEN
The lumen of the gastrointestinal tract is home to an enormous quantity of different bacterial species that thrive in an often symbiotic relationship with the host. It is the principal source of microbial products because of its massive bacterial load. Injury to the immune component of the gastrointestinal mucosal surface, along with damage to the intestinal epithelial microenvironment with its antimicrobial functions, may affect systemic immune activation during the chronic phase of HIV infection through the increased translocation of luminal microbial products. Moreover, microbial translocation, which is defined as "the passage of both viable and nonviable microbes and microbial products such as endotoxin across anatomically intact intestinal barrier", may be a fundamental mechanism through which HIV accelerates progression of chronic viral hepatitis. Improvements in the tools available to microbiota research, and especially advancement of our knowledge in this area may help us in controlling the evolution of HIV disease, although population complexity and diversity between individuals make this challenging.
Asunto(s)
Tracto Gastrointestinal/microbiología , Infecciones por VIH/microbiología , Progresión de la Enfermedad , Tracto Gastrointestinal/inmunología , Infecciones por VIH/inmunología , Humanos , Inmunidad Mucosa/inmunología , Mucosa Intestinal/inmunología , Mucosa Intestinal/microbiologíaRESUMEN
The pharmacokinetics and in dosing regimens of the currently available pegylated interferon (peginterferon) alfa molecules differ greatly, depending on the size and nature of their polyethylene glycol (PEG) moiety. Peginterferon alfa-2a has a branched 40 kDa PEG chain covalently attached to lysine residues and circulates as an intact molecule. On the other hand, peginterferon alfa-2b has a linear 12 kDa PEG chain covalently attached to interferon-a-2b via an unstable urethane bond that is hydrolysed after injection, releasing native interferon alfa-2b. The difference in pegylation between the two peginterferons has a significant impact on their pharmacokinetic properties. Data from comparative and non-comparative studies indicate that peginterferon alfa-2b has a shorter half-life in serum than peginterferon alfa-2a, and a significant proportion of patients receiving peginterferon alfa-2b may have trough concentrations below the limit of detection during the latter part of the 7-day dosing schedule. However, the pharmacodynamic parameters of the two drugs appear to be similar.
Asunto(s)
Antivirales/farmacocinética , Antivirales/uso terapéutico , Hepacivirus/efectos de los fármacos , Interferón-alfa/farmacocinética , Interferón-alfa/uso terapéutico , Polietilenglicoles/farmacocinética , Polietilenglicoles/uso terapéutico , Antivirales/farmacología , Ensayos Clínicos como Asunto , Quimioterapia Combinada , Semivida , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/virología , Humanos , Interferón alfa-2 , Interferón-alfa/farmacología , Polietilenglicoles/farmacología , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , Resultado del TratamientoRESUMEN
AIMS: To determine the variability of the prion protein gene (PRNP) in goats from Northern and Southern Italy. METHODS AND RESULTS: Genomic DNA isolated from goat blood was polymerase chain reaction (PCR)-amplified for the coding region of the PRNP gene and then sequenced. In total, 13 polymorphic sites were identified: G37V, T110P, G127S, M137I, I142M, I142T, H143R, R154H, P168Q, T194P, R211Q, Q222K and S240P (substitutions I142T and T194P are novel) giving rise to 14 haplotypes. Clear frequency differences between Northern and Southern breeds were found and confirmed by genetic distance analysis. CONCLUSIONS: Differences in allele distribution were found between Northern and Southern goats, in particular regarding the M142 and K222 alleles, possibly associated to scrapie resistance; philogeographical analysis supported the idea that Northern and Southern breeds may be considered as separate clusters. SIGNIFICANCE AND IMPACT OF THE STUDY: In Italy only limited studies have been carried out on caprine PRNP genotype distribution; this study is important to fill this lack of information. Moreover the finding of significant differences among allele distributions in Northern and Southern goats, especially if involved in modulating resistance/susceptibility, need to be carefully considered for the feasibility of selection plans for resistance to scrapie.
Asunto(s)
Cabras/genética , Polimorfismo Genético , Proteínas PrPSc/genética , Scrapie/genética , Animales , Cruzamiento , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Italia , Reacción en Cadena de la Polimerasa/veterinaria , Análisis de Secuencia de ADN/veterinariaRESUMEN
BACKGROUND: Peginterferon alpha-2a and alpha-2b, the two commercially available pegylated interferons, have different pharmacokinetic properties that produce differing abilities to suppress replication of the hepatitis C virus. AIM: To compare the pharmacodynamics of peginterferon alpha-2a and peginterferon alpha-2b in interferon-naive patients with chronic hepatitis C. METHODS: Patients were randomized to receive peginterferon alpha-2a, 180 microg (n = 10) or peginterferon alpha-2b 1.0 microg/kg (n = 12) once weekly. The enzymatic activity of 2'5'-oligoadenylate synthetase and levels of neopterin and beta(2)-microglobulin were measured at baseline and at 24, 48, 120 and 168 h. RESULTS: Oligoadenylate synthetase activity and serum neopterin and beta(2)-microglobulin concentrations did not differ significantly between the two patient groups at any time point, nor was there a significant correlation between the serum area under the concentration-time curve of either peginterferon and the area under the concentration-time curve for 2',5'-oligoadenylate synthetase, neopterin and beta(2)-microglobulin. The area under the concentration-time curves calculated for these three markers did not correlate with body mass index stratified at <25 and >or=25 kg/m(2) for either peginterferon. CONCLUSIONS: Despite pharmacokinetic differences between peginterferon alpha-2a and peginterferon alpha-2b, the pharmacodynamic profiles of the two formulations appear to be comparable.
Asunto(s)
Antivirales/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/farmacología , Polietilenglicoles/farmacología , Adulto , Femenino , Humanos , Interferón alfa-2 , Interferón-alfa/farmacocinética , Interferón-alfa/uso terapéutico , Masculino , Persona de Mediana Edad , Polietilenglicoles/farmacocinética , Polietilenglicoles/uso terapéutico , Proteínas Recombinantes , Resultado del TratamientoRESUMEN
An investigation was undertaken with the aim of studying the repetitive region of the MUC1 gene and analyzing its polymorphisms in some Italian sheep breeds. Two primers previously used for the goat MUC1 gene analyses allowed for the amplification of 4 different alleles. The sequence analysis showed that the repetitive region of the sheep MUC1 gene is an array of 60-bp repeats, in accordance with the information reported in humans, cattle, and goats. The polypeptide sequence encoded by the consensus repeat was very similar to the corresponding sequences of goats and cattle. The average homology of all repeated units was 82%; when the repeats were compared with the derived consensus repeat, homology dropped to 78%. The repeats were not all perfectly conserved, but the sequence homology was nevertheless clearly sufficient to preserve the mechanism giving rise to the variable-number tandem-repeat polymorphism. In spite of their reduced sequence homology, the sheep repeats shared a high number of potential glycosylation sites. The conservation of the exact number and position of glycosylation sites did not seem to be very important for the purpose of functional integrity, but glycosylation appeared to be conserved as a bulk property. Analysis of the polymorphism in 6 Italian breeds showed that the sheep repetitive region seemed to be less variable and smaller in size than the repetitive region of the goat. The findings of this study suggest that ruminants can be a useful model to study the mechanisms by which the variation in the repeat number and the extracellular domain size can modulate the effectiveness of MUC1 as a cell-surface shield.
Asunto(s)
ADN/genética , Mucina-1/genética , Polimorfismo Genético , Secuencias Repetitivas de Ácidos Nucleicos , Ovinos/genética , Alelos , Animales , Sitios de Unión , Clonación Molecular , Secuencia Conservada , ADN/sangre , ADN/química , Electroforesis en Gel de Poliacrilamida , Frecuencia de los Genes , Glicosilación , Italia , Repeticiones de Minisatélite , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Homología de Secuencia , Secuencias Repetidas en TándemRESUMEN
Highly active antiretroviral therapy including protease inhibitors has led to dramatic decrease in the morbidity and mortality resulting from infection with human immunodeficiency virus-1. However, this combination regimen can be associated with the occurrence of serious toxicities, which may reduce patient compliance. In particular, human immunodeficiency virus-1 protease inhibitors and nevirapine among nonnucleoside reverse transcriptase inhibitors, have the potential for producing hepatotoxicity. We summarise current knowledge of the hepatotoxic effects associated with the commercially available human immunodeficiency virus-1 protease inhibitors based on a literature review of the major retrospective and prospective clinical studies designed to elucidate risk factors for developing hepatotoxicity among human immunodeficiency virus-1-infected patients receiving antiretroviral therapy containing protease inhibitors. Coinfection with chronic hepatitis, a common occurrence in human immunodeficiency virus-1-infected patients, is identified as an independent risk factor for developing hepatotoxicity in antiretroviral-treated human immunodeficiency virus-1-infected patients treated with antiretroviral regimens containing protease inhibitors. The importance of other risk factors for developing protease inhibitor-associated hepatotoxicity and the mechanism underlying the drug-related hepatotoxicity are discussed. The data indicate that the potential for producing hepatotoxicity is variable among the protease inhibitors and suggest that based on differences in drug-related hepatotoxicity, certain protease inhibitors may be preferred for the treatment of human immunodeficiency virus-hepatitis C virus coinfected patients.
Asunto(s)
Terapia Antirretroviral Altamente Activa/efectos adversos , Inhibidores de la Proteasa del VIH/efectos adversos , Hígado/efectos de los fármacos , Monitoreo de Drogas , Inhibidores de la Proteasa del VIH/metabolismo , VIH-1/efectos de los fármacos , Humanos , Hígado/enzimología , Hígado/patología , Factores de RiesgoRESUMEN
Four bovine BAC clones (0494F01, 0069D07, 0060B06, and 0306A12) containing MUC1, as confirmed by mapping MUC1 on a RH3000 radiation hybrid panel, were hybridised on R-banded chromosomes of cattle (BTA), river buffalo (BBU), sheep (OAR) and goat (CHI). MUC1 was FISH-mapped on BTA3q13, BBU6q13, OAR1p13 and CHI3q13 and both chromosomes and chromosome bands were homoeologous confirming the high degree of chromosome homoeologies among bovids and adding more information on the pericentromeric regions of these species' chromosomes. Indeed, MUC1 was more precisely assigned to BTA3 and assigned for the first time to BBU6, OAR1p and CHI3. Moreover, detailed and improved cytogenetic maps of BTA3, CHI3, OAR1p and BBU6 are shown and compared with HSA1.
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Mapeo Cromosómico/métodos , Cromosomas Humanos Par 1 , Cromosomas de los Mamíferos , Mucina-1/genética , Animales , Secuencia de Bases , Bovinos , Células Cultivadas , Cartilla de ADN , Cabras , Humanos , Hibridación Fluorescente in Situ , Linfocitos/citología , Linfocitos/fisiología , OvinosRESUMEN
Characterization of Leishmania infantum is based on zymodeme analysis, which requires parasite isolation and therefore is not routinely employed. Moreover, the majority of strains in the Mediterranean Basin belong to zymodeme MON-1, and this is a major limitation for this technique in epidemiological studies in this region. We developed a PCR-RFLP method based on kDNA amplification, which was able to discriminate L. infantum strains directly from peripheral blood. Twenty-eight samples were tested with this technique: four obtained from promastigote cultures, and 24 collected from dogs (18) and human donors (six) from traditionally endemic and newly endemic areas of northwestern Italy. Extracted DNAs were amplified using RV1-RV2 primers and PCR products were digested using two restriction enzymes separately: BsiY I and Mlun NI. Some patterns were specific to certain areas. In particular, the identity of PCR-RFLP patterns from a human patient from a newly endemic area and three dogs allow the confirmation of the autochthonous origin of this case. This approach could be applied to epidemiological studies in order to trace the diffusion of L. infantum within dog populations, as well as its transmission to humans.
Asunto(s)
Enfermedades de los Perros/parasitología , Enfermedades Endémicas/veterinaria , Leishmania infantum/aislamiento & purificación , Leishmaniasis Visceral/veterinaria , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Animales , Secuencia de Bases , Enzimas de Restricción del ADN/genética , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/genética , Perros , Humanos , Italia/epidemiología , Leishmaniasis Visceral/genética , Leishmaniasis Visceral/parasitologíaRESUMEN
The aim of this work was to investigate the genetic structure of the casein gene cluster in 5 Italian goat breeds and to evaluate the haplotype variability within and among populations. A total of 430 goats from Vallesana, Roccaverano, Jonica, Garganica, and Maltese breeds were genotyped at alphas1-casein (CSN1S1), alphas2-casein, (CSN1S2), beta-casein (CSN2), and kappa-casein (CSN3) loci using several genomic techniques and milk protein analysis. Casein haplotype frequencies were estimated for each breed. Principal component analysis was carried out to highlight the relationship among breeds. Allele and haplotype distributions indicated considerable differences among breeds. The haplotype CSN1S1*F- CSN1S2*F-CSN3*D occurred in all breeds with frequencies >0.100 and was the most common haplotype in the Southern breeds. A high frequency of CSN1S1*0-CSN1S2*C-CSN3*A haplotype was found in Vallesana population (0.162). Principal component analysis clearly separated the Northern and Southern breeds by the first component. The variability of the caprine casein loci and variety of resulting haplotypes should be exploited in the future using specific breeding programs aiming to preserve biodiversity and to select goat genetic lines for specific protein production.
Asunto(s)
Cruzamiento , Caseínas/genética , Variación Genética , Cabras/genética , Familia de Multigenes , Animales , Femenino , Frecuencia de los Genes , Genotipo , Geografía , Haplotipos , Italia , Masculino , Reacción en Cadena de la Polimerasa/veterinaria , Análisis de Componente PrincipalRESUMEN
The objective of our study was to demonstrate the existence of a repetitive region in the goat MUC1 gene and to develop a polymerase chain reaction (PCR) protocol to analyze its polymorphism in different breeds. Using 2 primers derived from the bovine MUC1 sequence, a PCR fragment was obtained and cloned. The sequence analysis shows that the repetitive region of goat MUC1 is an array of 60 bp repeats in accordance with the data reported for other species. The polypeptide sequences encoded by the consensus repeats of goat and bovine were exactly alike. A PCR protocol to improve the detection of goat MUC1 polymorphism was developed, and a total of 178 animals from 6 Italian breeds were analyzed. Fifteen different alleles, ranging in size from 1500 to 3000 bp, were found. The high number of alleles observed shows that the goat MUC1 is a hypervariable gene. These results are the basis for further investigations on the possible role of MUC1 polymorphism in the genetic control of disease susceptibility and production traits in the goat species.
Asunto(s)
Cabras/genética , Mucina-1/genética , Polimorfismo Genético , Alelos , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bovinos , Secuencia de Consenso , Electroforesis en Gel de Agar , Frecuencia de los Genes , Humanos , Datos de Secuencia Molecular , Mucina-1/química , Reacción en Cadena de la Polimerasa , Secuencias Repetitivas de Ácidos Nucleicos , Alineación de SecuenciaRESUMEN
Hepatitis C virus-related liver disease and its associated complications are steadily emerging health concerns in persons co-infected with human immunodeficiency virus. The increasing number of liver-related deaths in human immunodeficiency virus-hepatitis C virus co-infected individuals supports the compelling argument for more aggressive treatment in these patients. The safety and efficacy of interferon/ribavirin in human immunodeficiency virus/hepatitis C virus co-infected patients is currently under evaluation. Despite well-documented concern over highly active antiretroviral therapy-associated hepatotoxicity human immunodeficiency virus/hepatitis C virus co-infected patients should be offered antiretroviral therapy. Since management of co-infected patients is complex a multidisciplinary approach is needed in order to facilitate care and help patients to achieve a positive outcome.
Asunto(s)
Infecciones por VIH/complicaciones , Hepatitis C/complicaciones , Terapia Antirretroviral Altamente Activa/efectos adversos , Antivirales/uso terapéutico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Esquema de Medicación , Interacciones Farmacológicas , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Humanos , Interferón-alfa/uso terapéutico , Ribavirina/uso terapéuticoRESUMEN
OBJECTIVE: To compare the plasma pharmacokinetics of lamivudine 150mg twice daily and 300mg once daily in patients with HIV-1 infection. DESIGN: Nonblind, sequential, pharmacokinetic study. PARTICIPANTS: 13 patients with HIV-1 infection (median age 36 years). METHODS: Patients were tested during twice daily and then once daily regimens of lamivudine. In both regimens, the total daily dose of lamivudine was identical (300 mg/day). Blood samples for pharmacokinetic analysis were taken over a 12-hour period after > or =7 days of twice daily administration, and again over a 24-hour period after 7 days of once daily administration,. RESULTS: 12 patients completed the study. Lamivudine pharmacokinetic parameters (mean +/- SD) after administration of 150mg twice daily were: peak plasma concentration (Cmax) 2077+/-816 microg/L; trough plasma concentration (Cmin) 332+/-219 microg/L; elimination half-life (t 1/2beta) 6.1+/-1.9h; time to Cmax (t(max)) 1.6+/-0.7h; average concentration over the dosage interval (Cav) 711+/-269 microg/L; and area under the concentration-time curve (AUC) over 2 dosage intervals (24h) 17085+/-6464 microg x h/L. Corresponding values after administration of 300mg once daily were: Cmax 3461+/-854 microg/L; Cmin 146+/-87 microg/L; t1/2 7.9+/-3.4h; t(max) 2.2+/-1.3h; Cav 705+/-177 microg/L; and AUC over 1 dosage interval (24h) 16644+/-4150 microg x h/L. Statistical analysis showed a significant difference (p < 0.05) between the 2 schedules for Cmax and Cmin values, whereas no significant differences emerged for the other parameters. CONCLUSIONS: Once daily lamivudine leads to a similar exposure in plasma as twice daily administration of the same total daily dose. Since once daily administration may result in improved compliance, these results provide the pharmacokinetic basis for using lamivudine in a once daily regimen. Randomised clinical studies are needed to confirm this pharmacokinetic finding.