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Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which preferentially inhibits cyclooxygenase-2 (COX-2) over cyclooxygenase-1 (COX-1). Gastrointestinal (GI) tolerability of meloxicam 7.5 and 15 mg vs piroxicam 20 mg was evaluated in a 4-week, double-blind, parallel group, placebo-controlled study in 51 healthy male volunteers, using a combination of oesphago-gastro-duodenal endoscopy, faecal blood loss measurement and symptom evaluation. Analysis of covariance found no significant difference in faecal blood loss between the groups. However, significantly higher bleeding was found with piroxicam 20 mg compared with placebo using a Student's t-test on the weighted means. Endoscopy score were significantly higher with piroxicam than with meloxicam 7.5 mg or placebo (P < 0.01). A significant difference from baseline was observed in the meloxicam 15 mg and piroxicam groups (P < 0.05), but not in the meloxicam 7.5 mg and placebo groups. Six piroxicam-treated volunteers were withdrawn following a poor endoscopic score, but no such withdrawals occurred in the meloxicam and placebo groups (P < 0.01). Meloxicam 7.5 mg caused less GI damage compared with piroxicam 20 when administered to healthy young volunteers for 28 days; a possible dose dependency effect in GI tolerability was also suggested for meloxicam 7.5 and 15 mg, in relation to endoscopic findings.

Therapeutic drug monitoring (TDM) should be adopted in all neonatal intensive care units (NICUs), where the most preterm and fragile babies are hospitalized and treated with many drugs, considering that organs and metabolic pathways undergo deep and progressive maturation processes after birth. Different developmental changes are involved in interindividual variability in response to drugs. A crucial point of TDM is the choice of the bioanalytical method and of the sample to use. TDM in neonates is primarily used for antibiotics, antifungals, and antiepileptic drugs in clinical practice. TDM appears to be particularly promising in specific populations: neonates who undergo therapeutic hypothermia or extracorporeal life support, preterm infants, infants who need a tailored dose of anticancer drugs. This review provides an overview of the latest advances in this field, showing options for a personalized therapy in newborns and infants.

The common practice of therapeutic drug monitoring (TDM) involves the quantification of drug plasma concentrations at a specific time in a dosing window. Although TDM for antibiotics is not considered mandatory, it may represent a valid tool for clinicians in order to limit antibiotic resistance and avoid therapeutic failures. The aim of our study was to develop and validate a high‐performance liquid chromatography–diode array detection method for simultaneous quantification of 10 antibiotics in plasma. This method has a fast analytical procedure that uses the same chromatographic conditions to quantify ceftazidime, ceftriaxone, meropenem, ertapenem, ciprofloxacin, tigecycline, ampicillin, levofloxacin and piperacillin, plus the β‐lactamase inhibitor tazobactam. Method validation was ensured by testing selectivity, accuracy, precision, limits of detection and quantification, recovery and stability. The calibration ranges, established accordingly to the expected plasma concentration in patients, showed a coefficient of determination >0.996 for all compounds. Within‐ and between‐days precisions reported a coefficient of variation >15%. Similarly, the accuracy evaluation reported a relative standard deviation of <10% for each antibiotic. The recovery ranged between 97 and 103% for all compounds. This method could represent a useful tool for TDM of antibiotics.

Background: Eltrombopag (EPAG) is an oral thrombopoietin receptor agonist, approved for refractory primary immune thrombocytopenia (ITP) in pediatric patients. In two pediatric RCTs, EPAG led to an improvement of platelet counts and a reduction in bleeding severity. However, a significant number of pediatric patients did not achieve the primary endpoints. We performed a pharmacokinetic evaluation of EPAG in pediatric patients with refractory ITP.Methods: Outpatients aged from 1 to 17 y, affected by refractory ITP to first-line treatment, were enrolled for a pharmacokinetic assessment. The analysis of drug plasma concentration was performed by the LC-MS/MS platform. Non-compartmental and statistical subgroup analyses were carried out using the R package ncappc.Results: Among 36 patients eligible for PK analysis, the median dose of EPAG given once daily was 50 mg. The EPAG peak occurs between 2 and 4 h with a population Cmax and AUC 0–24 geo-mean of 23, 38 μg/ml, and 275, 4 µg*h/mL, respectively. The pharmacokinetic profile of EPAG did not show a dose proportionality. Female patients showed a statistically significant increase of dose-normalized exposure parameters, increasing by 110 and 123% for Cmax and AUC 0–24, respectively, when compared to male patients. Patients aged 1–5 y showed values increased by more than 100% considering both exposure parameters, compared to older children. Furthermore, patients presenting complete response (83%), showed augmented EPAG exposure parameters compared to subjects with partial or no response.Conclusion: These data highlight the need to further explore the variability of EPAG exposure and its pharmacokinetic/pharmacodynamic profile in pediatric patients also in a real-life setting.

The object of this work was to compare the efficacy of antibiotic combinations including ceftriaxone with that of combinations including an antipseudomonal beta-lactam for the empirical treatment of febrile neutropenia in cancer patients. We identified all published randomised trials comparing two antibiotic combinations differing only in the beta-lactam, being ceftriaxone in one treatment group and an antipseudomonal beta-lactam in the other. The quality of individual trials was formally evaluated. A meta-analysis was performed using the Peto-modified Mantel-Haenszel method for combining binary data. Primary analysis was done, for both febrile episodes and bacteraemic episodes, using failure of empirical antibiotic treatment defined as modification of the initial allocated regimen or death during treatment. Secondary analysis was done using death from any cause in the two treatment groups. Data relating to 1,537 febrile neutropenic episodes recorded in eight randomised clinical trial were pooled s. Overall, there were 256 treatment failures out of 782 febrile episodes treated with ceftriaxone-containing combinations (32.7%), and 243 out of 755 treated with antipseudomonal beta-lactam regimens (32.1%). The pooled odds ratio of failure for ceftriaxone-containing combinations for febrile episodes was 1.04, with the 95% confidence interval ranging from 0.84 to 1.29, and that for bacteraemic episodes was 0.93 (95% confidence interval 0.58-1.49). With regard to overall mortality, there were 54 deaths among 782 febrile episodes treated with ceftriaxone-containing combinations (6.9%) and 62 deaths among 755 febrile episodes treated with antipseudomonal beta-lactam-containing regimens (8.2%). The pooled odds ratio of death for ceftriaxone regimens was 0.84 (95% confidence interval 0.57-1.24). Results of this meta-analysis show that in the empirical treatment of febrile neutropenia, antibiotic combinations containing ceftriaxone are as effective as those in which the beta-lactam has specific activity against Pseudomonas aeruginosa, such as ureidopenicillin or ceftazidime.

Aims and Background The necessity of an antiemetic prophylaxis in patients treated with chemotherapy of low emetogenic potential, such as 5-fluorouracil ± folinic acid fractionated over several consecutive days, is controversial. The aim of the study was to evaluate the therapeutic behavior of oncologists on this issue. Methods All consecutive in and out patients who started chemotherapy in 33 Italian oncological departments from June 24 to July 6, 1996, were studied. The antiemetic prescription pattern and its effectiveness, in patients submitted to 5-fluorouracil ± folinic acid were evaluated. Results Of the 1956 patients submitted to cancer chemotherapy, 259 patients received 5-fluorouracil ± folinic acid. Of these, 186 patients were treated for 5 consecutive days, 47 for 4 days, 20 for 3 days and 6 for 2 days. A total of 219 (84.5%) received an antiemetic prophylaxis: 43.4% a 5-HT3 antagonist ± steroids, 37.5% an antidopaminergic drug, 10.9% a steroid ± antidopaminergic drug, and 8.2% other drugs. Only 40 patients (15.5%) did not receive an antiemetic prophylaxis. Overall complete protection from vomiting/nausea was 225/259 (86.9%)/163/259 (62.9%). The complete protection from vomiting/nausea during the 5 days in the 186 patients was not significantly different among patients receiving or not an antiemetic prophylaxis (88.1%/64.9% vs 88.9%/55.6%). At unifactorial analysis, the previous experience of vomiting/nausea caused by chemotherapy was found to be a significant prognostic factor. In fact, overall complete protection from vomiting/nausea was significantly inferior in patients who had previous experience of vomiting/nausea (65.1%/35.0%) with respect to those who did not (91.2%/75.4%, P < 0.001/> 0.001, respectively). Conclusions. The study showed that in clinical practice patients submitted to 5-fluorouracil ± folinic acid obtained a similar high protection from vomiting and nausea regardless of whether or not antiemetic prophylaxis was given. It would be therefore reasonable not to treat patients undergoing such chemotherapy, whereas patients with previous experience of vomiting/nausea caused by chemotherapy should be given an antiemetic prophylaxis.

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