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.
Sáez-Llorens
Xavier
X
Hospital del Niño, Panama City, Panama. joseph_chow@merck.com
Macias
Mercedes
M
Maiya
Padmanabha
P
Pineros
Juan
J
Jafri
Hasan S
HS
Chatterjee
Archana
A
Ruiz
Gloria
G
Raghavan
Janaki
J
Bradshaw
Susan K
SK
Kartsonis
Nicholas A
NA
Sun
Peng
P
Strohmaier
Kim M
KM
Fallon
Marissa
M
Bi
Sheng
S
Stone
Julie A
JA
Chow
Joseph W
JW
D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001830:Body Surface Area; D002177:Candidiasis / Q000188:drug therapy; D000077336:Caspofungin; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D054714:Echinocandins / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005334:Fever / Q000139:chemically induced; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D006985:Hyperventilation / Q000139:chemically induced; D007223:Infant; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D055666:Lipopeptides; D008297:Male; D015337:Multicenter Studies as Topic; D011446:Prospective Studies
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin