Single-dose pharmacokinetics of ampicillin and tobramycin administered by hypodermoclysis in young and older healthy volunteers

Abstract

1. To test the feasibility of administering antibiotics by subcutaneous infusion to the elderly, we compared the pharmacokinetics of tobramycin (single dose of 80 mg) given by hypodermoclysis (HDC) with the kinetics of the antibiotic injected intravenously (i.v.) in 10 young (< 50 years old) and 10 elderly (> 65 years old) healthy volunteers. Similar studies were performed with ampicillin (single dose of 1 g) in 12 young and 10 older healthy volunteers. 2. Compared with the i.v. route, HDC delayed the time to reach the maximal plasma concentration (t(max)) of tobramycin in young volunteers: 32 ± 6 (s.d.) min vs 88 ± 46, P < 0.005, and older volunteers: 27 ± 4 min vs 89 ± 15, P < 0.005. Administration of the antibiotics by HDC was well tolerated. The plasma concentration of tobramycin 30 min after the end of infusion (C60) was lower (P<0.05) following HDC than after the i.v. route in both young, 2.2 ± 0.7 vs 3.5 ± 0.8 μg ml-1, and elderly subjects, 2.2 ± 0.8 vs 3.8 ± 0.9·μg ml-1. 3. The area under the curve (AUG) of tobramycin given by HDC was slightly smaller than when given i.v., i.e. in young subjects: 740±225 (s.d.) vs 893 ± 223 μg ml-1 min, NS, and in the elderly: 980 ± 228 vs 1056 ± 315 μg ml-1 min, NS. 4 When ampicilin was administered by HDC, the t(max) was also delayed in young volunteers: 45 ± 18 vs 23 ± 6 min, and in the elderly: 49 ± 18 vs 27 ± 4 min, P < 0.005, the AUC was greater by HDC than i.v. in the young volunteers: 4527 ± 1658 μgml-1 min us 3810 ± 1033 μg ml-1 min and in the elderly: 6795 ± 2094 μg ml-1 min vs 4217 ± 1518 μg ml-1 min, and the C60 was higher by HDC in the young: 27 ± 7 vs 24 ± 9 μg ml-1, and in the elderly: 32 ± 9 vs 23 ± 11 μg ml-1, P < 0.05. 5. In conclusion, HDC delays the entry of the antibiotic into the systemic circulation, but did not affect the amount available. HDC was well tolerated and could become an adequate method for antibiotic administration to the elderly.