Abstract
Solithromycin is a novel fluoroketolide antibiotic which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age, 6 years [age range, 4 days to 17 years]) were administered intravenous (i.v.) or oral (capsules or suspension) solithromycin (i.v., 6 to 8 mg/kg of body weight; capsules/suspension, 14 to 16 mg/kg on days 1 and 7 to 15 mg/kg on days 2 to 5). PK samples were collected after the first and multidose administration. Data from 83 subjects (662 samples) were combined with previously collected adolescent PK data (n 13; median age, 16 years [age range, 12 to 17 years]) following capsule administration to perform a population PK analysis. A 2-compartment PK model characterized the data well, and postmenstrual age was the only significant covariate after accounting for body size differences. Dosing simulations suggested that 8 mg/kg i.v. daily and oral dosing of 20 mg/kg on day 1 (800-mg adult maximum) followed by 10 mg/kg on days 2 to 5 (400-mg adult maximum) would achieve a pediatric solithromycin exposure consistent with the exposures observed in adults. Seventy-six treatment-emergent adverse events (TEAEs) were reported in 40 subjects. Diarrhea (6 subjects) and infusion site pain or phlebitis (3 subjects) were the most frequently reported adverse events related to treatment. Two subjects experienced TEAEs of increased hepatic enzymes that were deemed not to be related to the study treatment. (The phase 1 pediatric studies discussed in this paper have been registered at ClinicalTrials.gov under identifiers NCT01966055 and NCT02268279.)
| Original language | English (US) |
|---|---|
| Article number | e00692-18 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 62 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2018 |
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Keywords
- Antibiotics
- Pediatrics
- Pharmacokinetics
- Safety
- Solithromycin
ASJC Scopus subject areas
- Pharmacology
- Pharmacology (medical)
- Infectious Diseases
Cite this
Population pharmacokinetics and safety of solithromycin following intravenous and oral administration in infants, children, and adolescents. / SOLI-PEDS Program.
In: Antimicrobial Agents and Chemotherapy, Vol. 62, No. 8, e00692-18, 01.08.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Population pharmacokinetics and safety of solithromycin following intravenous and oral administration in infants, children, and adolescents
AU - SOLI-PEDS Program
AU - Gonzalez, Daniel
AU - James, Laura P.
AU - Al-Uzri, Amira
AU - Bosheva, Miroslava
AU - Adler-Shohet, Felice C.
AU - Mendley, Susan R.
AU - Bradley, John S.
AU - Espinosa, Claudia
AU - Tsonkova, Eva
AU - Moffett, Kathryn
AU - Marquez, Lucila
AU - Simonsen, Kari A.
AU - Stoilov, Stefan
AU - Boakye-Agyeman, Felix
AU - Jasion, Theresa
AU - Hornik, Christoph P.
AU - Hernandez, Robert
AU - Benjamin, Daniel K.
AU - Cohen-Wolkowiez, Michael
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Solithromycin is a novel fluoroketolide antibiotic which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age, 6 years [age range, 4 days to 17 years]) were administered intravenous (i.v.) or oral (capsules or suspension) solithromycin (i.v., 6 to 8 mg/kg of body weight; capsules/suspension, 14 to 16 mg/kg on days 1 and 7 to 15 mg/kg on days 2 to 5). PK samples were collected after the first and multidose administration. Data from 83 subjects (662 samples) were combined with previously collected adolescent PK data (n 13; median age, 16 years [age range, 12 to 17 years]) following capsule administration to perform a population PK analysis. A 2-compartment PK model characterized the data well, and postmenstrual age was the only significant covariate after accounting for body size differences. Dosing simulations suggested that 8 mg/kg i.v. daily and oral dosing of 20 mg/kg on day 1 (800-mg adult maximum) followed by 10 mg/kg on days 2 to 5 (400-mg adult maximum) would achieve a pediatric solithromycin exposure consistent with the exposures observed in adults. Seventy-six treatment-emergent adverse events (TEAEs) were reported in 40 subjects. Diarrhea (6 subjects) and infusion site pain or phlebitis (3 subjects) were the most frequently reported adverse events related to treatment. Two subjects experienced TEAEs of increased hepatic enzymes that were deemed not to be related to the study treatment. (The phase 1 pediatric studies discussed in this paper have been registered at ClinicalTrials.gov under identifiers NCT01966055 and NCT02268279.)
AB - Solithromycin is a novel fluoroketolide antibiotic which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age, 6 years [age range, 4 days to 17 years]) were administered intravenous (i.v.) or oral (capsules or suspension) solithromycin (i.v., 6 to 8 mg/kg of body weight; capsules/suspension, 14 to 16 mg/kg on days 1 and 7 to 15 mg/kg on days 2 to 5). PK samples were collected after the first and multidose administration. Data from 83 subjects (662 samples) were combined with previously collected adolescent PK data (n 13; median age, 16 years [age range, 12 to 17 years]) following capsule administration to perform a population PK analysis. A 2-compartment PK model characterized the data well, and postmenstrual age was the only significant covariate after accounting for body size differences. Dosing simulations suggested that 8 mg/kg i.v. daily and oral dosing of 20 mg/kg on day 1 (800-mg adult maximum) followed by 10 mg/kg on days 2 to 5 (400-mg adult maximum) would achieve a pediatric solithromycin exposure consistent with the exposures observed in adults. Seventy-six treatment-emergent adverse events (TEAEs) were reported in 40 subjects. Diarrhea (6 subjects) and infusion site pain or phlebitis (3 subjects) were the most frequently reported adverse events related to treatment. Two subjects experienced TEAEs of increased hepatic enzymes that were deemed not to be related to the study treatment. (The phase 1 pediatric studies discussed in this paper have been registered at ClinicalTrials.gov under identifiers NCT01966055 and NCT02268279.)
KW - Antibiotics
KW - Pediatrics
KW - Pharmacokinetics
KW - Safety
KW - Solithromycin
UR - http://www.scopus.com/inward/record.url?scp=85052020696&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052020696&partnerID=8YFLogxK
U2 - 10.1128/AAC.00692-18
DO - 10.1128/AAC.00692-18
M3 - Article
C2 - 29891609
AN - SCOPUS:85052020696
VL - 62
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 8
M1 - e00692-18
ER -