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

ABSTRACT

1To 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.

2Compared 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.

3The area under the curve (AUC) 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.

4When ampicillin 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  μg  ml⁻¹ min vs 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.

5In 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.