5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration.
In this study, the biodistribution of 5-aminolaevulinic acid (ALA) and accumulation of protoporphyrin IX (PpIX) in rats have been examined. Two groups of 21 WAG/Rij rats are given 200 mg/kg ALA orally or intravenously. Six rats serve as controls. At 1, 2, 3, 4, 6, 12 and 24 h after ALA administration, ALA and porphyrin concentrations are measured in 18 tissues and fluids. Liver enzymes and renal-function tests are measured to determine ALA toxicity. In both groups ALA concentration is highest in kidney, bladder and urine. After oral administration, high concentrations are also found in duodenal aspirate and jejunum. Mild, short-lasting elevation of creatinine is seen in both treatment groups. Porphyrins, especially PpIX, accumulate mainly in duodenal aspirate, jejunum, liver and kidney (> 10 nmol/g tissue), less in oesophagus, stomach, colon, spleen, bladder, heart, lung and nerve (2-10 nmol/g tissue), and only slightly in plasma, muscle, fat, skin and brain (< 2 nmol/g tissue). In situ synthesis of porphyrins rather than enterohepatic circulation contributes to the PpIX accumulation. Confocal laser scanning microscopy shows selective porphyrin fluorescence in epithelial layers. Peak levels and total production of porphyrins are equal after oral and intravenous ALA administration.


CONCLUSIONS
administration of 200 mg/kg ALA results in accumulation of photosensitive concentrations of PpIX, 1 to 6 h after ALA administration, in all tissues except muscle, fat, skin and brain. Knowledge of the time-concentration relationship should be helpful in selecting dosages, routes of administration and timing of ALA photodynamic therapy.
van den Boogert
J
J
Laboratory for Experimental Surgery, Erasmus University, Medical Faculty, Rotterdam, Netherlands. vandenboogert@heel.fgg.eui.nl
van Hillegersberg
R
R
de Rooij
F W
FW
de Bruin
R W
RW
Edixhoven-Bosdijk
A
A
Houtsmuller
A B
AB
Siersema
P D
PD
Wilson
J H
JH
Tilanus
H W
HW
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003404:Creatinine / Q000097:blood; D007275:Injections, Intravenous; D007677:Kidney Function Tests; D008297:Male; D018613:Microscopy, Confocal; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D011162:Porphobilinogen / Q000378:metabolism; D011524:Protoporphyrins / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D014508:Urea / Q000097:blood
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D011162:Porphobilinogen; D000622:Aminolevulinic Acid; D014508:Urea; D003404:Creatinine; C028025:protoporphyrin IX; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase