Pharmacokinetics and safety of caspofungin in neonates and infants less than 3 months of age.

Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data for neonates and very young infants. Patients of <3 months of age receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n = 6) or subsequent multiple-dose (n = 12) panel; all received caspofungin at 25 mg/m(2) once daily as a 1-hour infusion. Caspofungin plasma levels were measured by high-performance liquid chromatography and compared to historical data from adults. Patient chronological ages ranged from 1 to 11 weeks, and weights ranged from 0.68 to 3.8 kg. Gestational ages ranged from 24 to 41 weeks. Geometric mean (GM) peak (C(1 h)) and trough (C(24 h)) caspofungin levels were 8.2 and 1.8 microg/ml, respectively, on day 1, and 11.1 and 2.4 microg/ml, respectively, on day 4. GM ratios for C(1 h) and C(24 h) for neonates/infants relative to adults receiving caspofungin at 50 mg/day were 1.07 and 1.36, respectively, on day 1, and 1.18 and 1.21, respectively, on day 4. Clinical and laboratory adverse events occurred in 17 (94%) and 8 (44%) patients, respectively. Five patients (28%) had serious adverse events, none of which were considered drug related. Caspofungin at 25 mg/m(2) once daily was well tolerated in this group of neonates/infants of <3 months of age and appears to provide relatively similar plasma exposure to that obtained in adults receiving 50 mg/day. However, the small number of patients studied precludes any definitive recommendations about caspofungin dosing for this group comprising a broad range of ages and weights.

Panic disorder respiratory subtype: a comparison between responses to hyperventilation and CO2 challenge tests.

In this study 117 panic disorder patients were divided into a respiratory subtype group and a non-respiratory subtype group. The respiratory subtype patients were observed to be more sensitive to the 35% CO(2) inhalation challenge test and the hyperventilation test than the non-respiratory subtype patients.

Respiratory pattern in a rat model of epilepsy.

PURPOSE: Apnea is known to occur during seizures, but systematic studies of ictal respiratory changes in adults are few. Data regarding respiratory pattern defects during interictal periods also are scarce. Here we sought to generate information with regard to the interictal period in animals with pilocarpine-induced epilepsy. METHODS: Twelve rats (six chronically epileptic animals and six controls) were anesthetized, given tracheotomies, and subjected to hyperventilation or hypoventilation conditions. Breathing movements caused changes in thoracic volume and forced air to flow tidally through a pneumotachograph. This flow was measured by using a differential pressure transducer, passed through a polygraph, and from this to a computer with custom software that derived ventilation (VE), tidal volume (VT), inspiratory time (TI), expiratory time (TE), breathing frequency (f), and mean inspiratory flow (VT/TI) on a breath-by-breath basis. RESULTS: The hyperventilation maneuver caused a decrease in spontaneous ventilation in pilocarpine-treated and control rats. Although VE had a similar decrease in both groups, in the epileptic group, the decrease in VE was due to a significant (p < 0.05) increase in TE peak in relation to that of the control animals. The hypoventilation maneuver led to an increase in the arterial Paco2, followed by an increase in VE. In the epileptic group, the increase in VE was mediated by a significant (p < 0.05) decrease in TE peak compared with the control group. Systemic application of KCN, to evaluate the effects of peripheral chemoreception activation on ventilation, led to a similar increase in VE for both groups. CONCLUSIONS: The data indicate that pilocarpine-treated animals have an altered ability to react to (or compensate for) blood gas changes with changes in ventilation and suggest that it is centrally determined. We speculate on the possible relation of the current findings on treating different epilepsy-associated conditions.

Respiratory and acid-base parameters during salicylic intoxication in dogs.

This paper examines the mechanism responsible for hyperventilation and accompanying respiratory alkalosis during acute salicylism. Sodium salicylate (250 mg/kg) was administered to 8 spontaneously breathing anesthetized dogs (alpha-chloralose, 50 mg/kg, and urethane, 500 mg/kg, iv). The trachea was sectioned and connected to a pneumotachograph. A catheter was placed in the cisterna magna for sampling cerebrospinal fluid (CSF) and a femoral artery was cannulated for blood sampling and pressure determinations. Once the cardiorespiratory steady-state was obtained, air flow, tidal volume, arterial pressure, ECG and rectal temperature were measured for baseline control. The measurements were repeated 8 times during 100 min after salicylate infusion. Simultaneous determinations of CSF and plasma salicylate showed that plasmatic levels were maximal just after infusion, diminishing with time. CSF concentration increased gradually as the salicylate diffused through the blood-brain barrier. Minute ventilation increased to more than 600% of control values and was maximal between 60-100 min after salicylate infusion. Respiratory alkalosis and hyperthermia (up to 40.3 degrees C) followed the time-course of hyperventilation. Only a small part of hyperventilation can be attributed to the temperature increase. A high correlation coefficient (r = 0.974) was obtained by regression analysis of the values for ventilation and CSF salicylate. We conclude that the central action of salicylate is much more important for increasing ventilation than effects related to oxidative phosphorylation uncoupling.