PubMed Health⌕ Search

Biomedical subjects

C Manzanares

Publications and source records attributed to C Manzanares.

11 recordsLinked to original sources
PubMed2001

Covariate effects on the apparent clearance of tacrolimus in paediatric liver transplant patients undergoing conversion therapy.

OBJECTIVE: To analyse the influence of covariates on the apparent clearance (CL) of tacrolimus in paediatric liver transplant recipients being converted from cyclosporin to tacrolimus. DESIGN: Retrospective modelling study. PATIENTS AND PARTICIPANTS: 18 children, 13 girls and 5 boys, aged 4 months to 16 years (median 9.1 years) who required conversion to tacrolimus because of acute or chronic rejection or cyclosporin toxicity. METHODS: 287 whole-blood tacrolimus concentrations from therapeutic drug monitoring were used to build a nonlinear mixed-effects population model (NONMEM program) for the apparent clearance of tacrolimus. Variables considered were age, total bodyweight (TBW), body surface area (BSA), time after initiation of treatment (T), gender, haematocrit (Hct), albumin (Alb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (gammaGT), alkaline phosphatase (ALP), bilirubin (BIL), creatinine clearance (CL(CR)) and dosage of concomitant corticosteroids (EST). RESULTS: TBW, T, BIL and ALT were the covariates that displayed a significant influence on CL according to the final regression model: CL (L/h) = 10.4(TBW/70)3/4 x e(-0.00032 T) x e(-0.057 BIL) x (1 - 0.079 ALT). With this model, the estimates of the coefficients of variation were 24.3% and 29.5% for interpatient variability in CL and residual variability, respectively. CONCLUSIONS: The proposed model for tacrolimus CL can be applied for a priori dosage calculations, although the results should be used with caution because of the unexplained variability in the CL. We therefore recommended close monitoring of tacrolimus whole blood concentrations, especially within the first months of treatment. The best use of the model would be its application in dosage adjustment based on therapeutic drug monitoring and the Bayesian approach.

Adolescent↗
PubMed1998

Monitoring of tacrolimus as rescue therapy in pediatric liver transplantation.

The introduction of tacrolimus as rescue therapy represents a significant advance in the prevention of late graft failure and second liver transplantation. The authors report the blood level monitoring of tacrolimus as a rescue therapy in 21 children who underwent liver transplantation, and they report the dose-concentration relationship in the presence or absence of hepatitis C virus (HCV) in these patients. This was a retrospective study conducted from May 1993 to January 1997. Indication for the conversion from cyclosporine (CsA) to tacrolimus were acute rejection (62%), chronic rejection (33%), and CsA toxicity (5%). Mean daily dose in the first month was 0.32 mg/kg, whereas at the end of the follow-up period it was 0.14 mg/kg. Tacrolimus mean whole blood concentration levels were between 7.1 ng/ml and 9.4 ng/ml, without significant differences over time. Mean daily doses in HCV+ and HCV- patients were 0.08 and 0.24 mg/kg, respectively (p < 0.01), and mean concentrations were 8.3 and 8.4 ng/ml (NS). HCV+ children required a mean dose three times lower than the dose used in HCV- children to obtain the same tacrolimus trough blood level. Therefore, doses in HCV+ children must be decreased to achieve levels within the therapeutic range.

Adolescent↗
PubMed1998

Multicenter comparison of first- and second-generation IMx tacrolimus microparticle enzyme immunoassays in liver and kidney transplantation.

Tacrolimus is a potent immunosuppressive drug successfully used for baseline and rescue immunosuppression in patients after liver and kidney transplantation. Data from several clinical trials have demonstrated the efficacy of tacrolimus in the prevention of allograft rejection, even at lower concentrations in the therapeutic range (5-15 microg/L). In fact, some patients with tacrolimus levels at less than 5 microg/L have excellent hepatic or kidney function. The limit of detection of the IMx Tacrolimus I assay (TAC I; Abbott Laboratories, IL) is only 5 microg/L and that of the lower tacrolimus calibrator is 10 microg/L. The second-generation assay uses the same monoclonal antibody and the same IMx technology but offers improved sensitivity, with a dynamic range from 0 microg/L to 30 microg/L (lower calibrator, 3 microg/L). The aim of this multicenter study was to evaluate the new IMx Tacrolimus II assay (TAC II) by assessing its precision, sensitivity, performance, and correlation degree relative to the IMx TAC I assay. The study was performed at three centers in Spain. The within-run coefficients of variation (CVs) obtained for the new assay, using each of the trilevel controls in replicates of 20 during 3 consecutive days, were 8.06%, 4.38% and 5.09% at 5 microg/L, 11 microg/L, and 22 microg/L, respectively. The corresponding between-run CVs obtained measuring each of the three controls in duplicate on 10 consecutive days were 9.54%, 6.38% and 5.75%. The limit of detection, with 97.5% confidence, was 1.22 microg/L. TAC II results (Y) were compared with those from the original TAC I assay (X) analyzing 293 whole blood samples from liver (n=145) and kidney (n=148) transplant recipients. The correlation study with patient samples (using the Passing-Bablock method) was y=1.056, x + 0.017, r=0.927. No statistically significant differences were observed between assays (TAC I versus TAC II) in the mean values obtained for total patients (9.89+/-5.42 microg/L versus 10.49+/-5.63 microg/L), liver patients (9.16+/-4.79 microg/L versus 10.00+/-5.20 microg/L), and kidney patients (10.62+/-5.87 micro g/L versus 10.98+/-5.99 microg/L). The new IMx TAC II assay demonstrated the same precision and accuracy that characterized the original assay but showed improved sensitivity to the demands of tacrolimus monitoring in the lower therapeutic range of drug concentrations.

Antibodies, Monoclonal↗
PubMed1995

Guided tissue regeneration in severe periodontal defects in anterior teeth. Case reports.

Four consecutive chronic, severe periodontal bone defects in anterior teeth were treated by guided tissue regeneration, using a polytetrafluoroethylene periodontal membrane. The root surface was not specifically conditioned, and osseous grafts were not used. However the membrane was manipulated so that space under it was maintained. This was accomplished by painting the outer surface of the membrane with butyl-cyanoacrylate, so that it became rigid. The membranes were removed after 4 weeks and a bone-like tissue was found in all cases. The clinical results suggest that there was a relationship between the amount and quality of the new tissue and the volumetric characteristics of the available space.

Adult↗
PubMedDate not supplied

[Stability of theophylline in mono- and multi-layer parenteral nutrition bags].

The addition of drugs to parenteral nutrition (PN) presents a high risk of physical and chemical incompatibilities. In certain patients with water restriction or limited vein access, however, it may be necessary to add medicines to PN. Although there are numerous studies into the stability of aminophylline in PN, all of them refer to periods of less than 2 days. The purpose of the present study is to determine the stability of anhydrous theophylline over 24 hours at room temperature in 24 hours parenteral nutrition and over five days (four days stored in refrigerator and 24 hours at room temperature). In addition, to assess whether its degradation is affected by the use of single-layer or multi-layer bags. The composition of PN corresponds to a standard 1,800 Kcal diet at our hospital with a concentration of 0.164 mg/ml of anhydrous theophylline. No statistically significant differences were obtained in any of the cases studied, thus demonstrating the stability of theophylline under our study conditions both after 24 hours at room temperature and after four days of storage in the refrigerator followed by 24 hours at room temperature. Nor were differences found between storing the drug in single-layer and multi-layer bags.

Drug Packaging↗
PubMedDate not supplied

Therapeutic drug monitoring of tacrolimus: a moving matter.

Tacrolimus is a calcineurin inhibitor immunosuppressant that has been widely used in the last decade. The recommended doses and therapeutic ranges have changed from the beginning because now new combinations of immunosuppressants are used and the tendency is to maintain low tacrolimus levels in order to avoid undesirable side effects. As there is a great pharmacokinetic variability between patients we have a pediatric liver transplant protocol to calculate the area under the curve (AUC) in order to avoid over-immunosuppression in patients with risk of lymphoproliferative disorder. We have studied the influence of hepatitis C virus infection (HCV) on tacrolimus requirements in patients with kidney transplant, and we observed that HCV+ patients need lower tacrolimus doses to maintain the same level as HCV-patients. These studies clearly contribute to improving drug effectiveness and thus to achieving an adequate immunosuppressive therapy.

Adult↗