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 (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 mg ml−1, and elderly subjects, 2.2±0.8 vs 3.8±0.9. mg ml−1. 3 The 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 mg ml−1 min, NS, and in the elderly: 980±228 vs 1056±315 mg ml−1 min, NS. 4 When 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 mg ml−1 min vs 3810±1033 mg ml−1 min and in the elderly: 6795±2094 mg ml−1 min vs 4217±1518 mg ml−1 min, and the C 60 was higher by HDC in the young: 27±7 vs 24±9 mg ml−1, and in the elderly: 32±9 vs 23±11 mg 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.

The development and evaluation of a subcutaneous infusion delivery system based on osmotic pump control and gas drive

“…Subcutaneous infusion is now a frequently selected infusion route used for opioid drugs in hospitals (Herndon & Fike, 2001;Justad, 2009), and it is also an effective way in treating diabetes (Hirsch et al, 2005;Fujikawa et al, 2012), cancer (Leahy et al, 1992;Befon et al, 2000), bacterial infections (Champoux et al, 1996), gastrointestinal obstruction (De Conno et al, 1991) and primary immunodeficiency deficiencies (Kirmse 2009;Wasserman et al, 2012). Such administration way, allowing patients to manage their own infusions at home, is also very suitable for ambulatory outpatients.…”

Administração de antibióticos por via subcutânea: uma revisão integrativa da literatura

“…Para a Ampicilina e Tobramicina (24) , a via SC modificou ligeiramente os parâmetros farmacocinéticos de ambos os antibióticos. Pequenas mudanças foram observadas na absorção, distribuição e eliminação, quando comparadas às vias SC e IV, que não desaconselharam seu uso por via SC.…”

“…Pesquisa realizada com os antibióticos Ampicilina e Tobramicina (24) confirmou que houve boa tolerância local por via SC nos sujeitos da pesquisa, sugerindo a utilidade potencial dessa via de administração para antibióticos, contudo apresenta ressalvas de que mais estudos são necessários, a fim de definir precisamente a dose de segurança.…”

“…A dose terapêutica usual para o Ceftriaxona é de 1 g, mas ficou evidenciado que com 0,5 g há melhor tolerância, porém essa dose não alcança índices terapêuticos (21) . Sendo assim, os Aminoglicosídeos tiveram pior tolerância local por via SC, apenas para a Tobramicina (24) não houve relato de intolerância. As Cefalosporinas apresentaram dados discordantes, de acordo com a dose empregada: no estudo com melhor tolerância, foi utilizada uma dose menor e lidocaína, simultaneamente.…”

“…Cabapenêmicos Ertapenem (22) Cefalosporinas 3ª geração Ceftriaxona (8,19,20,21) 4ª geração Cefepime (9) Glicopeptídeos Teicoplanina (23) Penicilinas Ampicilina (24) Aminoglicosídeos Tobramicina (24) Amicacina (25,26) Netilmicina (33) Gentamicina (28,29,30,31,32) Sisomicina (32) …”