SINGLE-DOSE PHARMACOKINETICS OF AMPICILLIN AND TOBRAMYCIN ADMINISTERED BY HYPODERMOCLYSIS IN YOUNG AND OLDER HEALTHY-VOLUNTEERS

1 To test the feasibility of administering antibiotics by subcutaneous infusion to the elderly, we compared the pharmacokinetics of tobramyc in (single dose of 80 mg) given by hypodermoclysis (HDC) with the kine tics of the antibiotic injected intravenously (i.v.) in 10 young (< 50 years old) and 10 elderly (> 65 years old) healthy volunteers. Simila r studies were performed with ampicillin (single dose of 1 g) in 12 yo ung and 10 older healthy volunteers. 2 Compared with the i.v. route, H DC 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 plas ma concentration of tobramycin 30 min after the end of infusion (C-60) 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 mu g ml(-1), and elderly subjects, 2 .2 +/- 0.8 vs 3.8 +/- 0.9. mu g ml(-1). 3 The area under the curve (AU G) of tobramycin given by HDC was slightly smaller than when given i.v ., i.e. in young subjects: 740 +/- 225 (s.d.) us 893 +/- 223 mu g ml(- 1) min, NS, and in the elderly: 980 +/- 228 vs 1056 +/- 315 mu g ml(-1 ) min, NS. 4 When ampicillin was administered by HDC, the t(max) was a lso 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 mu g ml(-1) min vs 3810 +/- 1033 mu g ml(-1) min and in the elderly: 6795 +/- 2094 mu g ml(-1) min vs 4217 +/- 1518 mu g ml(-1) min, and the C-60 was higher by HDC in the young: 27 +/- 7 vs 24 +/- 9 mu g ml(-1), and in the eld erly: 32 +/- 9 us 23 +/- 11 mu g ml(-1), P < 0.05. 5 In conclusion, HD C delays the entry of the antibiotic into the systemic circulation, bu t did not affect the amount available. HDC was well tolerated and coul d become an adequate method for antibiotic administration to the elder ly.