摘要:

Lidocaine (LID) is an aminoethylamide used in hepatology to perform the monoethylglycinexylidide (MEGX) test for the evaluation of liver function in patients with cirrhosis (CIR) or chronic hepatitis (CH). The authors evaluated whether the MEGX test changes psychometric performance in patients with chronic liver disease and, in particular, whether it might trigger subclinical portosystemic encephalopathy in patients with CIR. Thirty patients with CIR and 20 patients with CH were studied. They underwent a standard-dose MEGX test, before and after which a psychometric test was administered and blood pressure, heart rate, and adverse effects were recorded. The MEGX test did not modify psychometric performance. Mean arterial blood pressure and heart rate did not change at the end of the MEGX test in either patients with CH or CIR. Adverse effects were present in 66% of all patients during lidocaine injection and lasted up to 3 minutes afterwards. They were more frequent in patients with CH than in patients with CIR (85% vs 53%). No relationship was found between adverse effects and lidocaine dosage, nor between adverse effects and MEGX or lidocaine concentration at 15 minutes. Standard-dose MEGX test does not worsen or trigger portosystemic encephalopathy in CIR. Adverse effects were frequent but mild.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Nineteen pediatric patients affected by acute lymphoblastic leukemia (ALL) were examined weekly with respect to 6-mercaptopurine nucleotide (6-MPN) and 6-thioguanine nucleotide (6-TGN) levels in erythrocytes during the course of maintenance treatment with 6-MP 50 mg/m2per d and results were related to various parameters of bone marrow function to assess, in the same individual, the level of reliability of 6-MP metabolites in predicting a later change in peripheral blood cell counts. Median values for 6-MPN and 6-TGN were 57 and 200 pmol/8 × 108erythrocytes, respectively, as measured by reversed-phase high-performance liquid chromatography (HPLC). 6-TGN levels in erythrocytes were inversely related with white blood cell count (r= −0.463, p < 0.0001, n = 361), absolute neutrophil count (r= −0.386, p < 0.0001, n = 347), erythrocyte (r= −0.354, p < 0.0001, n = 287), and platelet counts (r= −0.24, p < 0.0001, n = 319) in the majority of patients (n = 10–12), while no correlation was found for 6-MPN. In the remaining children, no evidence of correlation was demonstrated between 6-TGN levels and myelotoxicity. The results confirm the role of 6-TGN as the reference cytotoxic metabolite for evaluating the exposure to 6-MP and identifying treatment compliance in ALL children but indicate the limits of a follow-up based solely on metabolite levels and suggest that a more correct approach remains the double monitoring of 6-TGN and blood cell count with differential.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The authors report a possible interaction between ketobemidone and busulfan during myeloablative treatment of a patient with acute myeloid leukemia. At the time of admission, the patient was receiving ketobemidone 1,000 mg/d as analgesic for a rectal fissure. The patient started conditioning prior to bone marrow transplantation with busulfan (1 mg/kg × 4 for 4 days). High busulfan plasma concentrations were observed after the first dose and the next doses were reduced to 0.7 mg/kg. The kinetics of both drugs revealed that an increase in ketobemidone concentration was followed by an increase in busulfan levels. Substituting ketobemidone with morphine resulted in a decrease in busulfan concentration despite increasing the dose once more to 1 mg/kg.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Ciprofloxacin is a fluoroquinolone antibiotic effective in the treatment of lower respiratory tract infections (LRTI). The aim of this study was to assess the pharmacokinetic appropriateness of a standard switch iv/os regimen of ciprofloxacin (200 mg iv bid for 3 to 5 days followed by 500 mg os bid for 7 to 10 days) frequently used in routine clinical practice in the treatment of elderly patients with mild to moderate LRTI. The pharmacokinetic study was performed on a cohort of 17 elderly inpatients. Blood samples were collected in steady state conditions at appropriate intervals. Ciprofloxacin serum concentrations were analyzed using an HPLC method and pharmacokinetic parameters were estimated using the WinNonlin software package. The pharmacokinetic data were at least partially different from those obtained by other authors in elderly patients (lower Cmaxafter iv administration and higher CL both after iv and oral administration). Cmaxafter a 1-hour 200-mg infusion were similar to those observed during the 500 mg bid peroral regimen (2.1 ± 0.9 mg/L vs 2.6 ± 1.0 mg/L ; p = 0.054). The absolute oral bioavailability (84.1%) allowed a total body exposure 2.1-fold greater after 500 mg bid oral administration than after 200 mg bid iv administration (AUC0-&tgr;11.4 ± 4.3 mg/L·h vs 5.5 ± 1.8 mg/L·h). The results show that in malabsorption-free elderly patients a regimen of 500 mg os bid may be considered a valid therapeutic approach from the beginning of therapy for mild to moderate LRTI caused by sensitive microrganisms (MIC < 0.1 mg/L). In fact, because the peak serum level to MIC ratio (Cmax/MIC) and the area under the inhibitory serum concentration-time curve (AUIC24= AUC24h/MIC) are actually considered major pharmacodynamic determinants for the outcome of treatment with fluoroquinolones, this regimen could guarantee both a better pharmacokinetic exposure than the 200 mg iv bid regimen and a cost-effective treatment of LRTI. However, because of the great pharmacokinetic interindividual variability observed a normalized dosage per kg (3 mg/kg/12h iv and 8 mg/kg/12h os) should be considered, especially for body weight >90 kg and, whenever possible, TDM of AUC0-&tgr;or at least of Cmaxshould be performed to individualize therapy in this subpopulation.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The authors we investigated the relationship between plasma levels of haloperidol (HAL) and the number ofCYP2D6*10(*10)alleles in 66 Japanese inpatients with schizophrenia (male = 61, female = 5) on HAL. Plasma HAL level was determined by an enzyme immunoassay method. Daily dose of HAL was 1.5–36 (mean ± SD = 12.3 ± 7.6) mg or 0.02–0.49 (0.21 ± 0.13) mg/kg body weight. Plasma HAL levels ranged from 1.4 to 47.4 (12.4 ± 9.5) ng/mL. No significant difference in the plasma HAL levels was observed between the subjects with no, one, and two*10alleles (one-way analysis of variance: 56.1 ± 20.3, 61.0 ± 20.3, and 63.3 ± 20.3 ng/mL/mg/kg , respectively, F(2,63) = 0.65, p = 0.52). These results are not supportive of the previous report that plasma HAL levels can be predicted by the number of*10alleles in Asian patients.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Thioridazine is metabolized in humans by CYP2D6 to mesoridazine, which is an active metabolite. Two or more CYP2D6 substrates are seldom given simultaneously to elderly patients because potentially dangerous metabolic interactions may occur. It may be valuable to know the CYP2D6 metabolic capacity of such patients to avoid drug interactions, which depend on the metabolic phenotype. The goal of this study was to evaluate the use of the mesoridazine/thioridazine ratio for the estimation of CYP2D6 enzyme capacity. A sensitive and reliable method has been developed for the determination of thioridazine and its metabolites, mesoridazine and sulforidazine. Commonly used central nervous system (CNS) comedications do not interfere with the method. A group of 27 chronic patients with mental illness receiving monotherapy with thioridazine were studied. There were 23 men and 4 women between 37 and 80 years old (mean ±SD: 61.2 ± 10.2). The thioridazine/mesoridazine ratio correlated with the debrisoquine metabolic ratio (r= 0.74, p < 0.001). Therefore, the authors suggest that the measurement of thioridazine and its metabolite might be a useful tool to assess CYP2D6 activity during treatment.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The relationship between ritonavir plasma concentration, efficacy, and tolerance was evaluated in 31 children with advanced HIV infection who were receiving a triple therapy with ritonavir as protease inhibitor. Median CD4+lymphocyte count and median viral load before the initiation of ritonavir-containing combination therapy were 1320 cells/mL and 5 log10 copies/mL, respectively. Ritonavir was given at a dose ranging from 300 to 450 mg/m2twice daily. The median follow-up of triple therapy was 19 months. Response was defined as a drop of viremia of more than 1 log. Plasma drug levels were determined twice during the observation period: after at least 4 weeks and after 3 months of combined treatment. Samples were collected before (residual) and 2 hours (T2) after drug intake. Cholesterol, triglycerides, alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase were assessed at the same time. The median values of ritonavir residual and T2 levels were 1.64 mg/L and 5.9 mg/L at observation 1 and 3.35 mg/L and 6.29 mg/L at observation 2, respectively. According to virologic response, median residual concentrations of ritonavir were 3.17, 2.52, and 1.04 mg/L for the complete, the partial, and the no-response groups. The authors observed a wide intersubject variability of ritonavir concentrations with an increase in residual levels between the two observation periods. Residual levels were correlated with virologic response whereas there was no direct association between T2 levels and long-term response. Patients with complete or partial response displayed statistically significantly higher residual concentrations than the no-response group. No correlation could be demonstrated between elevated plasma drug concentrations and abnormal cholesterol or triglycerides values. These results emphasize the importance of a sustained high ritonavir concentration to achieve optimal treatment efficacy. Furthermore, these results prove the clinical benefit of therapeutic drug monitoring and could potentially improve patient evaluation in terms of treatment efficacy, compliance, and viral resistance.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Twenty-five healthy volunteers were given 100 mg caffeine orally and several estimates of cytochrome P450 1A2 (CYP1A2) activity were evaluated. The validation was performed by correlation of different parameters in plasma, saliva, and urine to two measures of caffeine clearance, CLoraland CL137X→17Xthat served as standards of reference. Two subjects were excluded because of noncompliance with a caffeine-free diet. In the remaining 23 subjects, both plasma and saliva total clearances of caffeine were highly correlated with each other (rs= 0.97, p < 0.0001). The ratio 17X/137X restricted to one sampling point taken 4 hours after dose, showed a high correlation (rs) with CLoraland CL137X→17Xin plasma (0.84 / 0.83) and saliva (0.82 / 0.77) (p < 0.0001 for all the correlation values) where 17X is 1,7-dimethylxanthine (paraxanthine) and 137X is 1,3,7-trimethylxanthine (caffeine). Additionally, the ratio (AFMU + 1U + 1X + 17U + 17X)/137X in a 0–24 hours urine sampling showed the highest correlation with CL137X→17X(rs= 0.85, p < 0.001) where AFMU is 5-acetylamino-6-formylamino-3-methyluracil, 1U is 1-methyluracil, 1X is 1-methylxanthine, and 17U is 1,7-dimethyluric acid. The major estimates of CYP1A2 activity were significantly less in nonsmoking females, and this probably was related to the use of oral contraceptives in this subpopulation. In summary, among caffeine-based approaches for CYP1A2, the authors recommend either plasma or saliva 17X/137X ratio and the urinary (AFMU + 1U + 1X + 17U + 17X)/137X ratio during a sampling interval of at least 8 hours, starting at time zero since caffeine intake. These indices are simple, reliable, and relatively inexpensive estimates of CYP1A2 activity to be used in the study of human populations.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Fenfluramine and phentermine (`fen-phen') are stimulants used primarily for weight loss that have a causative association with serious health problems. Though voluntarily removed from the market by their manufacturers and the FDA in September of 1997, both drugs occasionally reappear in the clinical and forensic setting from individuals who retained old prescriptions, transported the drugs from foreign countries, or `stockpiled' the medications immediately before their removal from the market. The authors describe an analytical method for simultaneous detection of fenfluramine, phentermine, and the internal standard,N-propylamphetamine, in urine using pentafluoropropionic anhydride derivatization. Detection using and mass spectrometry is described. Baseline resolution of the analytes was achieved in the presence of four other common sympathomimetic amines. The increased molecular weights, better peak profiles, and characteristic fragments containing portions of both derivatizing agent and parent compound aid in the unambiguous identification of these analytes.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

The effects of storage time (0 – 8 days), temperature (4°C and 30°C in dark and light), and freeze-thaw cycles on the stability of sirolimus in blood were examined. Sirolimus quantification was undertaken using HPLC-electrospray-tandem mass spectrometry. Whole blood samples supplemented with sirolimus (5.0, 15.0, and 30.0 &mgr;g/L) and pooled renal and heart transplant samples were found to be stable during the 8 days under all conditions (<10% decrease in concentration). No significant difference was observed in sirolimus concentration between freshly collected patient samples and sirolimus-supplemented samples (5.0, 15.0, and 30.0 &mgr;g/L) after three freeze-thaw cycles (p > 0.198). In conclusion, blood samples can be transported with or without cooling for up to 8 days without sirolimus results being compromised. The reanalysis of sirolimus samples, which may entail freeze-thaw cycles, can be undertaken if the number of cycles is three or less.

ISSN:0163-4356    

出版商:OVID    

年代:2000

数据来源: OVID