Elimination of aluminum adjuvants.
In vitro dissolution experiments although perhaps not at typical body concentrations and temperatures demonstrated that the alpha-hydroxycarboxylic acids present in interstitial fluid (citric acid, lactic acid, and malic acid) are capable of dissolving aluminum-containing adjuvants. Amorphous aluminum phosphate adjuvant dissolved more rapidly than crystalline aluminum hydroxide adjuvant. Intramuscular administration in New Zealand White rabbits of aluminum phosphate and aluminum hydroxide adjuvants, which were labelled with 26Al, revealed that 26Al was present in the first blood sample (1 h) for both adjuvants. The area under the blood level curve for 28 days indicated that three times more aluminum was absorbed from aluminum phosphate adjuvant than aluminum hydroxide adjuvant. In vivo studies using 26Al-labelled adjuvants are relatively safe because accelerator mass spectrometry (AMS) can quantify quantities of 26Al as small as 10(-17) g. A similar study in humans would require a whole-body exposure of 0.7 microSv per year compared to the natural background exposure of 3000 microSv per year. The in vitro dissolution and in vivo absorption studies indicate that aluminum-containing adjuvants which are administered intramuscularly are dissolved by alpha-hydroxycarboxylic acids in interstitial fluid, absorbed into the blood, distributed to tissues, and eliminated in the urine.
Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, IN 47907, USA. hem@pharmacy.purdue.edu
Stanley L
SL
Hem
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics*; D000535:Aluminum / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D005110:Extracellular Space / Q000378:metabolism; D005260:Female; D006801:Humans; D011817:Rabbits; D012995:Solubility
D000276:Adjuvants, Immunologic; D000535:Aluminum