Abstract
Protoporphyrin accumulates in tissues after administration of δ-aminolevulinic acid, and can be used as a photosensitizer for photodynamic therapy. To determine the distribution of porphyrins in a large animal model after administration of this porphyrin precursor, δ-aminolevulinic acid was administered to anesthetized dogs (100 mg/kg body weight intravenously) and porphyrin concentrations were measured in tissues (liver, pancreas, prostate, bladder, muscle and skin), plasma and urine for 6-10 h. Porphyrins increased markedly (up to 50-fold) in plasma within 1 h, were still markedly increased at 8 h, and consisted mostly of coproporphyrin III and protoporphyrin. Tissue porphyrin concentrations increased more slowly, were highest in liver, pancreas and prostate 7-10 h after δ-aminolevulinic acid administration, and were predominantly protoporphyrin. Maximum porphyrin concentrations in liver were 3- and 4-fold higher than in pancreas and prostate, respectively. Urinary δ-aminolevulinic acid excretion increased and was greatest 2-4 h after dosing; urinary porphobilinogen and porphyrins increased more gradually and remained increased up to at least 8 h. Coproporphyrin III was the predominant porphyrin in urine at all times, but hepta-, hexa- and pentacarboxyl porphyrins increased proportionally after administration of δ-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of δ-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 362-370 |
| Number of pages | 9 |
| Journal | Pharmacology |
| Volume | 52 |
| Issue number | 6 |
| State | Published - Jun 1996 |
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Keywords
- δ-aminolevulinic acid
- Cancer
- Photodynamic therapy
- Porphyrins
- Protoporphyrin
ASJC Scopus subject areas
- Pharmacology
Cite this
Accumulation of porphyrins in plasma and tissues of dogs after δ-aminolevulinic acid administration : Implications for photodynamic therapy. / Egger, Norman G.; Motamedi, Massoud; Pow-Sang, Mariela; Orihuela, Eduardo; Anderson, Karl.
In: Pharmacology, Vol. 52, No. 6, 06.1996, p. 362-370.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Accumulation of porphyrins in plasma and tissues of dogs after δ-aminolevulinic acid administration
T2 - Implications for photodynamic therapy
AU - Egger, Norman G.
AU - Motamedi, Massoud
AU - Pow-Sang, Mariela
AU - Orihuela, Eduardo
AU - Anderson, Karl
PY - 1996/6
Y1 - 1996/6
N2 - Protoporphyrin accumulates in tissues after administration of δ-aminolevulinic acid, and can be used as a photosensitizer for photodynamic therapy. To determine the distribution of porphyrins in a large animal model after administration of this porphyrin precursor, δ-aminolevulinic acid was administered to anesthetized dogs (100 mg/kg body weight intravenously) and porphyrin concentrations were measured in tissues (liver, pancreas, prostate, bladder, muscle and skin), plasma and urine for 6-10 h. Porphyrins increased markedly (up to 50-fold) in plasma within 1 h, were still markedly increased at 8 h, and consisted mostly of coproporphyrin III and protoporphyrin. Tissue porphyrin concentrations increased more slowly, were highest in liver, pancreas and prostate 7-10 h after δ-aminolevulinic acid administration, and were predominantly protoporphyrin. Maximum porphyrin concentrations in liver were 3- and 4-fold higher than in pancreas and prostate, respectively. Urinary δ-aminolevulinic acid excretion increased and was greatest 2-4 h after dosing; urinary porphobilinogen and porphyrins increased more gradually and remained increased up to at least 8 h. Coproporphyrin III was the predominant porphyrin in urine at all times, but hepta-, hexa- and pentacarboxyl porphyrins increased proportionally after administration of δ-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of δ-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.
AB - Protoporphyrin accumulates in tissues after administration of δ-aminolevulinic acid, and can be used as a photosensitizer for photodynamic therapy. To determine the distribution of porphyrins in a large animal model after administration of this porphyrin precursor, δ-aminolevulinic acid was administered to anesthetized dogs (100 mg/kg body weight intravenously) and porphyrin concentrations were measured in tissues (liver, pancreas, prostate, bladder, muscle and skin), plasma and urine for 6-10 h. Porphyrins increased markedly (up to 50-fold) in plasma within 1 h, were still markedly increased at 8 h, and consisted mostly of coproporphyrin III and protoporphyrin. Tissue porphyrin concentrations increased more slowly, were highest in liver, pancreas and prostate 7-10 h after δ-aminolevulinic acid administration, and were predominantly protoporphyrin. Maximum porphyrin concentrations in liver were 3- and 4-fold higher than in pancreas and prostate, respectively. Urinary δ-aminolevulinic acid excretion increased and was greatest 2-4 h after dosing; urinary porphobilinogen and porphyrins increased more gradually and remained increased up to at least 8 h. Coproporphyrin III was the predominant porphyrin in urine at all times, but hepta-, hexa- and pentacarboxyl porphyrins increased proportionally after administration of δ-aminolevulinic acid. These results indicate that porphyrins accumulate in plasma as well as tissues and urine after administration of δ-aminolevulinic acid, and may contribute to tumor necrosis during photodynamic therapy.
KW - δ-aminolevulinic acid
KW - Cancer
KW - Photodynamic therapy
KW - Porphyrins
KW - Protoporphyrin
UR - http://www.scopus.com/inward/record.url?scp=0029824659&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029824659&partnerID=8YFLogxK
M3 - Article
C2 - 8844786
AN - SCOPUS:0029824659
VL - 52
SP - 362
EP - 370
JO - Pharmacology
JF - Pharmacology
SN - 0031-7012
IS - 6
ER -