MITOTOX

Drug

D0474 | ritonavir

Properties

Molecular Formula	X
Molecular Weight	X
Structure
State	solid
Route of elimination	The metabolites are detected in the urine and feces.
Protein binding	Highly protein-bound, 98-99% [A19647].
Half life	3-5 hours [A19647].
Absorption	The absolute bioavailability of ritonavir has not been determined.
Trade names	Norvir
Description	antiretroviral; HIV protease inhibitor

Therapeutic Classification Source: DrugBank

J

J05AR23 Atazanavir and ritonavir

[J05AR] Antivirals for treatment of HIV infections, combinations

[J05A] DIRECT ACTING ANTIVIRALS

[J05] ANTIVIRALS FOR SYSTEMIC USE

[J] Antiinfectives for systemic use

J05AR10 Lopinavir and ritonavir

[J05AR] Antivirals for treatment of HIV infections, combinations

[J05A] DIRECT ACTING ANTIVIRALS

[J05] ANTIVIRALS FOR SYSTEMIC USE

[J] Antiinfectives for systemic use

J05AP53 Ombitasvir, paritaprevir and ritonavir

[J05AP] Antivirals for treatment of HCV infections

[J05A] DIRECT ACTING ANTIVIRALS

[J05] ANTIVIRALS FOR SYSTEMIC USE

[J] Antiinfectives for systemic use

J05AP52 Dasabuvir, ombitasvir, paritaprevir and ritonavir

[J05AP] Antivirals for treatment of HCV infections

[J05A] DIRECT ACTING ANTIVIRALS

[J05] ANTIVIRALS FOR SYSTEMIC USE

[J] Antiinfectives for systemic use

J05AE03 Ritonavir

[J05AE] Protease inhibitors

[J05A] DIRECT ACTING ANTIVIRALS

[J05] ANTIVIRALS FOR SYSTEMIC USE

[J] Antiinfectives for systemic use

Mitochondrial Toxicity Evaulation

Toxicity	Dose	Time	Species	Model	Method	Action	Positive criterion	Reference
MEMBRANE POTENTIAL	24.8 µM	30 mins	mouse	liver mitochondria	Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss)	decrease	EC20	36
RESPIRATION	35.5 µM	60 mins	mouse	liver mitochondria	Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition.	decrease	EC20	36
RESPIRATION	ND	60 mins	mouse	liver mitochondria	Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition.	Negative	EC20	36
ELECTRON TRANSPORT CHAIN						decrease		36
SWELLING	ND	30 mins	mouse	liver mitochondria	swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling )	Negative	EC20	36

Targets

Target	Dose	Time	Species	Model	Method	Action	Positive criterion	Reference
NADH:ubiquinone reductase	35.5 µM	60 mins	mouse	liver mitochondria	Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition.	inhibit	EC20	36
Succinate dehydrogenase	ND	60 mins	mouse	liver mitochondria	Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition.	Negative	EC20	36
Cytochrome c		30 mins	mouse	liver mitochondria	Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline)	Negative	EC20	36

Indications Source: SIDER

External IDs

DrugBank Name	Ritonavir
DrugBank	DB00503

References