Comparison of the pharmacokinetics, safety and tolerability of daptomycin in healthy adult volunteers following intravenous administration by 30 min infusion or 2 min injection.
OBJECTIVE
Two randomized Phase I studies in separate populations of healthy adult volunteers investigated the pharmacokinetics, safety and tolerability of daptomycin (Cubicin; Novartis Pharma AG, Basel, Switzerland) administered as a 2 min intravenous (iv) injection, relative to the currently licensed 30 min iv infusion.


METHODS
Study 1 was an open-label, single-dose, two-period, crossover study in which each subject received 6 mg/kg daptomycin administered as a 30 min iv infusion (n = 15) and as a 2 min iv injection (n = 16). In Study 2, a single-blind, multiple-dose, parallel-group study, subjects received a once-daily 2 min iv injection of 6 mg/kg daptomycin (n = 12), 4 mg/kg daptomycin (n = 8) or placebo (n = 4) for 7 days. Single-dose pharmacokinetics were assessed at various timepoints up to 36 and 24 h post-dose in Study 1 and Study 2, respectively, and multiple-dose pharmacokinetics were assessed in Study 2 at day 7 for 48 h post-dose.


RESULTS
In Study 1, pharmacokinetic comparability between the two administration regimens was demonstrated by meeting the bioequivalence criteria for the exposure parameters, AUC(0-t), AUC(0-infinity) and C(max). In Study 2, time-invariant pharmacokinetic properties as well as dose-proportional pharmacokinetics were demonstrated for the daptomycin 2 min iv injection regimen. In both studies, daptomycin was well tolerated and the majority of treatment-emergent adverse events were of mild intensity and considered to be unrelated to daptomycin.


CONCLUSIONS
The similar pharmacokinetic and safety profiles of the two administration regimens suggest that the 2 min iv injection may be a convenient treatment option for both patients and healthcare professionals.
Chakraborty
Abhijit
A
Novartis Institutes for Biomedical Research, East Hanover, NJ, USA. abhijit.chakraborty@novartis.com
Roy
Sandip
S
Loeffler
Juergen
J
Chaves
Ricardo L
RL
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D017576:Daptomycin / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D005260:Female; D006805:Human Experimentation; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010919:Placebos / Q000008:administration & dosage; D013557:Switzerland; D055815:Young Adult
D000900:Anti-Bacterial Agents; D010919:Placebos; D017576:Daptomycin