Aminoglutethimide | Cabergoline | Etomidate | Ketoconazole | Metyrapone | |
---|---|---|---|---|---|
Trade name; sponsoring company | Orimeten; Novartis | Dostinex; Pfizer | Hypnomidate; Janssen-Cilag | Nizoral; Janssen-Cilag | Metopirone; HRA Pharma |
European birth date | January 18, 1984 | June 24, 2002 | October 27, 1978 | July 20, 1981 | April 1, 1979 |
Cancer indication | Metastatic breast cancer | No | No | No | No |
Cmax (μg/mL) | 5.91 | 37 ± 8 pg/mL | N/A | 3.5 | 3.72 |
tmax (h) | 1.0 - 4.0 | 0.5 – 4.0 | N/A | 1.0 - 2.0 | 1.0 |
Bioavailability (oral, %) | 92 – 98 systemic | N/A3[28] | N/A | N/A | N/A |
Concomitant food intake effect on bioavailability | With food and water | No significant food effect | N/A | Maximal absorption with food | Recommended with milk or after a meal to minimize nausea and vomiting |
Volume of distribution (L/kg) 70-kg subject assumed | N/A | N/A3[28] | 4.5 | N/A | N/A |
Major metabolites | N-acetylaminoglutethimide (N-hydroxylaminoglutethimide **if enzyme induction occurs) | 6-Allyl-8-β-carboxy-ergoline | N/A | Main metabolism is by oxidation and cleavage of the imidazole- and piperazine-ring systems by hepatic microsomal enzymes. | Metyrapol, an active alcohol metabolite, similar potency in inhibiting adrenal 11-β-hydroxylase |
Plasma half-life (h) | 12.5 ± 1.6 | 63 - 69 | 3 - 5 | biphasic 2/8 | 20 - 26 minutes intravenous, ~2 h oral |
Plasma protein binding (%) | 21 – 25 | 41 - 424 | 76.5 | 99 (measured in vitro) mainly albumin | N/A |
Empirical formula (g/mol) | C13H16N2O2 (232.3) | C26H37N5O2 (451.6) | C14H16N2O2 (244.3) | C26H28Cl2N4O4 (531.4) | C14H14N2O (226.3) |
Mechanism of action | Inhibitor of cytochrome P450 (steroidogenesis and mineralocorticoidgenesis inhibitor) | Dopamine receptor agonist | Inhibits cortisol synthesis by inhibiting CYP11B1, and cytochrome P450scc [29] | Inhibitor of various subtypes of cytochrome P450 (steroidogenesis inhibitor);Inhibitor of side-chain cleavage complex, 17,20-lyase, 11-β-hydroxylase, 18- hydroxylase and 17-α-hydroxylase | Inhibits adreno-corticosteroid synthesis by blocking the 11-β-hydroxylase in the adrenal cortex |
Clinical recommended dose | Adrenocortical-adenoma: 2 - 3 × 250 mg adrenocortical-carcinoma: 2 - 4 × 250 mg ectopic ACTH-syndrome: 4 - 7 × 250 mg | Initiation of therapy: 0.25 mg twice a week. Dosage may be increased by 0.25 mg twice a week up to a dosage of 1 mg twice a week according to the patient’s serum prolactin level | Effective hypnotic dose: between 0.15 mg/kg and 0.30 mg/kg; doses of 0.04 – 0.05 mg/kg per h for hypercortisolemia patients [30] | 1 × 200 mg q.d. | Daily dose: from 250 mg to 6 g; 6 four-hourly doses of 15 mg/kg, with a minimum dose of 250 mg5 |
Dosage form | Tablet | Tablet | Solution | Tablet | Capsule |
Human AUC at the clinical dose | 96.8 ng*h/mL | 1295 ± 359.3 ng*h/mL [28] | N/A | N/A | N/A |
Mifepristone | Mitotane | Pasireotide | Temozolomide | ||
Trade name; sponsoring company | Corluxin; HRA Pharma | Lysodren; HRA Pharma | Signifor; Novartis | Temodal; Merck Sharp & Dohme | |
European birth date | August 25, 1999 | April 28, 2004 | April 24, 2012 | January 26, 1999 | |
Cancer indication | No | Adrenocortical carcinoma | No | Glioblastoma | |
Cmax (μg/mL) | 1.98 | 13.06[31] | N/A | 13.97[32] | |
tmax (h) | 1.0 - 2.0 | 3.76[31] | 0.25 - 0.5 | 0.5 – 1.5 | |
Bioavailability (oral, %) | 69 absolute by lower dose; higher dose 40 | N/A | N/A | Essentially 1007[32] | |
Concomitant food intake effect on bioavailability | No significant food effect | With food and water | N/A | No information in SmPC | |
Volume of distribution (L/kg) 70-kg subject assumed | 1.47 ± 0.25 [33] | N/A | Vz/F >100 Liter | 0.397[32] | |
Major metabolites | RU 42633, RU 42698 and RU 42848 | 1,1-(o,p’-Dichlorodiphenyl-) ethanoic acid (o,p’-DDA) | N/A | 5-Amino-imidazole-4-carboxamide (AIC) and Methyl-hydrazine | |
Plasma half-life (h) | 90 | 18 - 159 days | ~12 | 1.8 | |
Plasma protein binding (%) | 98 | N/A | 88 | 10 - 20 | |
Empirical formula (formula weight g/mol) | C29H35NO2 (429.6) | C14H10Cl4 (320.0) | C59H67N9O9 (1046.2) | C6H6N6O2 (194.2) | |
Mechanism of action | Competitive progesterone receptor antagonist | Precise mechanism of action is not known, but an adrenal inhibition is suspected | Binding to four of five somatostatin receptors; (SSTR-1,-2,-3,-5) [34] | After poisoning of TMZ to active metabolite MTIC, alkylation of Guanine-residues at N-7 | |
Clinical recommended dose | 600 mg | Patients are titrated to reach 14 - 20 mg/L plasma concentration starting with 2 - 3 g daily | 0.6 mg b.i.d. (0.3 or 0.9 mgdose adaption)8 | Initially 200 mg/m2 daily (pretreated patients: 150 mg/m2 daily) | |
Dosage form | Tablet | Tablet | Subcutaneous injection | Capsule | |
Human AUC at the clinical dose | 0.67 ± 0.21 μmol/l*h/mg9[35] | N/A | 54.1 ± 7.0 ng*h/mL10[36] | 33.2 μg*h/mL12[32] |