Pharmacokinetics of DepoFoam gentamicin delivery system and effect on soft tissue infection.
Infections of burn and soft tissue wounds are often difficult to treat with systemic antibiotics since drug delivery to the wound may be suboptimal and high doses may result in toxicity. DepoFoam particles, a novel lipid-based drug delivery system, are composed of phospholipid membranes, enclosing multiple aqueous chambers into which pharmacologic agents can be encapsulated for local drug delivery. We encapsulated gentamicin (GENT) in DepoFoam particles with an average yield of 81% +/- 8 SD for 10 preparations. Encapsulated GENT was incubated in human plasma with t1/2 of 21 days, demonstrating stability in vitro. In vivo pharmacokinetics were determined by injecting CF-1 mice subcutaneously (sc) with a single dose of 0.5 mg of free (nonencapsulated drug) or DepoFoam GENT. At intervals postinjection the sc tissue was excised and blood was obtained by inferior cava puncture and both were assayed for GENT levels. At 0.5, 2, 6, and 24 hr following drug administration there was a significant difference between GENT levels in the tissue achieved with the encapsulated drug and free drug with n = 3-4 at each time point for each group (P < 0.01). By 24 hr following administration of free drug there was minimal detectable GENT in the tissues, while therapeutic levels of GENT remained in tissue at 24 hr following DepoFoam GENT injection. Serum GENT peaked at 30 min for both the DepoFoam (5 micrograms/ml) and free drug (10 micrograms/ml) and was undetectable by 2 hr (n = 3 each group).(ABSTRACT TRUNCATED AT 250 WORDS)
Grayson
L S
LS
Department of Surgery, University of California, San Diego Medical Center 92103.
Hansbrough
J F
JF
Zapata-Sirvent
R L
RL
Kim
T
T
Kim
S
S
D000818:Animals; D002214:Capsules; D015169:Colony Count, Microbial; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D051379:Mice; D008863:Microspheres; D010743:Phospholipids; D013203:Staphylococcal Infections / Q000188:drug therapy*
D002214:Capsules; D005839:Gentamicins; D010743:Phospholipids