Atorvastatin-related rhabdomyolysis and acute renal failure in a genetically predisposed patient with potential drug-drug interaction.
METHODS
A 75-year-old man developed rhabdomyolysis and acute renal failure during atorvastatin therapy. All medications were discontinued and the patient was treated with intermittent hemodialysis throughout the course of hospitalization. After four weeks, patient's kidney function tests and serum myoglobin levels decreased to normal values and muscle weakness gradually disappeared. Genotyping results showed that the patient had a single-nucleotide polymorphism within genes encoding the organic anion-transporting polypeptide 1B1 and ATP binding cassette sub-family B member 1, which predisposed him for statin-induced myopathy. He was also a poor metabolizer of cytochrome P450 2C19. Concomitant therapy with pantoprazole could have resulted in the inhibition of cytochrome P450 3A4-mediated metabolism of atorvastatin and contributed to the development of rhabdomyolysis.


CONCLUSIONS
The case illustrates the clinical relevance and relationship between pharmacogenetic and pharmacokinetic factors in the development of statin-induced myopathy.
Department of Clinical Pharmacology, University Hospital Dubrava, Av. Gojka Suska 6, 10000, Zagreb, Croatia. srmarusic@inet.hr
Srecko
S
Marusic
Ante
A
Lisicic
Ivica
I
Horvatic
Vesna
V
Bacic-Vrca
Nada
N
Bozina
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000009:adverse effects; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D000069059:Atorvastatin; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects; D020022:Genetic Predisposition to Disease; D006538:Heptanoic Acids / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000378:metabolism; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D027361:Organic Anion Transporters / Q000235:genetics; D000077402:Pantoprazole; D020641:Polymorphism, Single Nucleotide; D054328:Proton Pump Inhibitors / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects* / Q000378:metabolism; D006435:Renal Dialysis; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D012307:Risk Factors; D016896:Treatment Outcome
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D054328:Proton Pump Inhibitors; D011758:Pyrroles; C503999:SLCO1B1 protein, human; D000069059:Atorvastatin; D000077402:Pantoprazole; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human