Table 1.
A Brief Pharmacokinetic Data of Potential Drugs Used in COVID-19 Management20
| Anti-COVID-19 Agent | Bioavailability (F) | Volume of Distribution (Vd) | Elimination half-life (T ½) | Clearance (Cl) | Distribution | Metabolism | Route of Elimination |
|---|---|---|---|---|---|---|---|
| Chloroquine (CQ) | 67–114% | 200–800 L/kg | 20 to 60 days | 0.35–1 L/h/kg | Wide distribution to many body tissues containing the heart, kidneys, liver, eyes, leukocytes, and lungs. It could obtain prolonged deposition in the lungs. | Partially hepatic to the main metabolite, desethylchloroquine. Metabolized by CYP2C8a, CYP3A4, and to a lesser extent CYP2D6. |
Predominantly eliminated in the urine. |
| Hydroxy chloroquine (HCQ) | 67–74% | 63 L/kg | 20 to 120 days | 5.76 L/h | In comparison with chloroquine, it has a more limited distribution to body tissues. | Hepatic; metabolites include bidesethylchloroquine, desethylhydroxychloroquin, and desethylchloroquine Metabolized by CYP2C8, CYP3A4, and to a lesser extent CYP2D6 |
40–50% is excreted renally |
| Lopinavir | 25% | 1–1.5 L/kg | 6.9 ± 2.2 hours | 6–7 L/h | It could be distributed to body tissues except the brain.21 | Hepatic via CYP3A4; 13 metabolites identIfied; may induce its own metabolism | Primarily eliminated in the feces (82.6 ± 2.5%) and the remaining excreted in the urine. |
| Ritonavir | Variable; increased with food. | 0.41 ± 0.25 L/kg | 3 to 5 hours | 8.8 ± 3.2 L/h | It could obtain a high concentration in plasma and lymph nodes but limited distribution to body tissues. | Hepatic via CYP3A4 and 2D6; five metabolites, low concentration of an active metabolite (M-2) achieved in plasma (oxidative) | Primarily eliminated in the feces (86.4 ± 2.9%) and the remaining excreted in the urine. |
| Atazanavir | 60–68%; enhanced with food. | 1.4 L/kg | 7 hours (increased to 12 hours in hepatically impaired patients) |
9.4 L/h | It has a highly variable distribution into body fluids.22 | Hepatic metabolism via CYP3A, also undergoes biliary elimination. | Primarily eliminated in the feces (79%) |
| Interferon-alpha | IM: 83% SubQ: 90% |
1.4 L/kg | 2 to 3 hours | 0.231 L/h/kg | It has wide distribution to body tissues especially in patients with leukemia (up to 20-folds). Interferon alpha could not penetrate CSFb. | Primarily renal, filtered and absorbed at the renal tubule | Renal clearance |
| Umifenovir | Rapid absorption | Not available | 17 to 21 hours | 99 ± 34 L/h | It has rapid absorption and distribution to different organs and tissues.23 | Mainly metabolized by the liver, it should be used with caution in patients with liver dysfunction. | The major route of elimination is via the feces |
| Favipiravir | 97.6% | 11–13.7 L/kg | 2 to 5.5 hours | 2.98±0.30 L/h | It may present rapid uptake and clearance from the liver, kidneys, and intestine during first dose administration. But in multiple-dose administration, plasma concentration may be diminished while drug distribution and accumulation in the liver, stomach, and brain would be enhanced significantly.24 | A genetic variant in digestive transport [Pgpkc; ABCB1d] and metabolism [aldehyde oxydase] to an inactive M1, urinary excretion; both metabolized by and inhibited by aldehyde oxidase | Predominantly renal clearance |
| Remdesivir | Not available | Not available | 0.39 hour | Not available | It has rapid distribution in PBMCse and conversion to its active form.25 | Predominantly metabolized to a triphosphate metabolite. | Not available |
| Tocilizumab | SubQ: 80% | 0.054 L/kg | Concentration-dependent; up to 16 days |
Concentration-dependent; Mean: 0.29 ± 0.10 mL/h/kg |
It might distribute to lymphatic, hematopoietic, digestive, endocrine, muscular, neural, respiratory, urinary systems, etc.26 Vd in adults is up to 2-folds in children. | Not available | Biphasic elimination from the circulation |
| Ivermectin | Well absorbed; Improved absorption with high fat meal. | 3 to 3.5 L/kg | 16 to 18 hours | 1.2 L/h | It may obtain high drug concentration in liver and adipose tissues, but has poor penetration through blood brain barrier. | Primarily hepatic metabolism. | Metabolized in the liver; ivermectin and/or its metabolites are excreted almost exclusively in the feces, Urine (<1%) |
| Teicoplanin | Oral: poorly absorbed IM: 90% |
0.86 L/kg | 70 to 100 hours | 0.0033 L/h/kg | Tissue distribution of teicoplanin is highly variable. It may present extensive distribution to liver tissue but poor penetration into CSF.27 | Metabolic transformation due to hydroxylation in the omega-2 and omega-1 positions for metabolites 1 and 2, respectively, of the C-10 linear side chain of component A2-3. | Not available |
| Azithromycin | 37% | 31.1 L/kg | 68 hours | 37.8 L/h | Extensively distributed to body tissues including skin, tonsil, lungs, sputum, etc. but has poor distribution to brain tissues due to limited CSF penetration. | Hepatic metabolism to inactive metabolites | Biliary excretion (major route) Urine (<6%) |
Notes: aCytochrome P450 (CYP) 2C8. b Cerebrospinal fluid. cP-glycoprotein. dATP-binding cassette sub-family B member 1. ePeripheral blood mononuclear cells.