TABLE A1.
Comprehensive table of anticholinergic drugs with pharmacokinetic considerations for age, sex, and CYP polymorphism
| Generic drug name | ACB 1 | ARS 2 | ADME 3 | Effect of | ||
|---|---|---|---|---|---|---|
| Sex on ADME | Age on ADME | Genetics on ADME | ||||
| Alprazolam | 1 |
F: approximately 90% Distribution: 80%, mostly to albumin Metabolism: Liver, extensive via CYP3A Renal clearance: 371 ml/h Renal excretion: 80% Fecal excretion: 7% TBC: 76 ml/min T 1/2: After oral administration to healthy adults 11.2 h |
The weight‐normalized clearance of alprazolam is 20%–30% higher in young women than in young men | Renal clearance is significantly decreased in elderly men | ||
| Amantadine | 2 | 2 |
F: 86%–94% Distribution: 59%–67% bound to serum proteins V d: 404 L or 4.9 L/kg Metabolism: Liver, extensive via CYP3A Renal clearance: 371 ml/h Renal excretion: 80% Fecal excretion: 0.6% TBC: 0.2–0.3 L/h/kg T 1/2: 17 (±4) h |
Amantadine has significantly higher renal clearance in men | Reduced clearance in elderly patients and reduced renal function: 22.6–45 h | |
| Amitriptyline | 3 | 3 |
F: high Metabolism: Liver, CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 T 1/2: 15 h (range: 9–25 h) |
Amitriptyline plasma levels were higher in women than in men | 1.5‐fold higher ratio of absolute serum concentration to dose adjusted serum concentration in the oldest age group in comparison to controls <40 years of age | |
| Atenolol | 1 |
F: 46%–60% Distribution: <5% bound to serum proteins, brain tissue:blood concentration ratio of 0.2:1 V d: 50–75 L Metabolism: No liver metabolism and no active metabolites Renal excretion: 40%–50% Fecal excretion: 50% T 1/2: 6–7 h |
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| Atropine | 3 | 3 |
F: high Distribution: Serum protein binding is highly variable by age: 22.5% ±20.6% (<16 years), 14% ±9.1% (16–58 years), 22.2% ±16.7% (65–75 years) V d: 3.3–3.9 L/kg T 1/2: 4 h (adults), 6.5 h (children) |
Protein binding is highly variable upon age, t 1/2 varies by age | ||
| Baclofen | 2 |
F: 100% V d: 59.1 L Metabolism: Liver, limited Renal clearance: 103 ml/min Renal excretion: 69%–85% of oral dose Fecal excretion: 10% TBC: 180 ml/min T 1/2: 3–6.8 h |
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| Benztropine | 3 | 3 | F: poor | |||
| Brompheniramine | 3 |
V d: 11.7 L/kg Metabolism: Liver, extensive Renal excretion: 17% T 1/2: 25 h |
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| Bupropion | 1 |
Distribution: 84% bound to serum proteins, CSF concentration 10–25 fold higher than plasma V d: 19–21 L/kg Metabolism: Liver, extensive, primarily CYP2B6 Renal excretion: 87% Fecal excretion: 10% TBC: 160 ml/h (±23%) T 1/2: 14–21 h |
Mean AUC and C Max for bupropion are higher in women than men however once these parameters are standardized for body weight the statistical significance is lost | In older adults (mean age 71.5 years) the clearance was 80% that seen in younger adults and the elimination t 1/2 was extended to 34 h compared with most sources which report 11–14 h | ||
| Captopril | 1 |
F: 70%–75% Distribution: 25%–30% bound to serum proteins V d: 0.7 L/kg Metabolism: Liver, 50% Renal clearance: 0.4 L/kg/h Renal excretion: 95% TBC: 0.8 L/kg/h T 1/2: 1.9 h |
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| Carbamazepine | 2 |
F: 70%–79% Distribution: 76% bound to serum proteins, the CSF/serum ratio 0.22 V d: 0.8–2 L/kg Metabolism: Liver, 98%, extensive via CYP3A4, inducer of CYP3A4 and CYP1A2 Renal excretion: 72% Fecal excretion: 28% TBC: 80 ml/min T 1/2: 12–17 h |
Patients 70 years and older had a decreased clearance by approximately 70% | |||
| Cetirizine | 1 | 2 |
F: rapid and complete Distribution: 93% bound to serum proteins V d: 0.5–0.8 L/kg Metabolism: Liver, minimal Renal excretion: 60% Fecal excretion: 10% TBC: 53 ml/min T 1/2: 7.4–9 h |
The t 1/2 is prolonged by 50% in older adults and in patients with chronic liver disease as compared with normal healthy adults | ||
| Chlorpheniramine | 3 | 3 |
F: good V d: 3.2 L/kg Metabolism: Liver, extensive Renal excretion: 50% Fecal excretion: <1% TBC: 234–470 ml/h/kg T 1/2: 20 h |
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| Chlorpromazine | 3 | 3 |
F: 32% Distribution: 90%–99% bound to serum proteins, CSF concentration 5 times the plasma concentration V d: 8–160 L/kg Metabolism: Liver, large extent Renal excretion: 23% T 1/2: 6 h |
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| Cimetidine | 1 | 2 | ||||
| Clomipramine | 3 |
F: 20%–78% Distribution: 97% bound to serum proteins, mostly albumin, CSF:plasma ratio is 2.6 V d: 7–20 L/kg Metabolism: Liver, extensive Renal excretion: 51%–60% Fecal excretion: 24%–32% TBC: 12.7–56.5 L/h T 1/2: 19–37 h |
The ratio of absolute serum concentration in comparison with the dose‐adjusted serum concentration is 1.1‐ to 1.5‐fold higher in women than in men, which suggests a dose reduction of 10%–30% for females | There is a 1.5‐fold higher ratio of absolute serum concentration to dose adjusted serum concentration in the oldest age group in comparison to controls <40 years of age | ||
| Clozapine | 3 |
F: 50%–60% Distribution: 97% bound to serum proteins V d: 6 L/kg Metabolism: Liver, extensive via CYP2D6, CYP1A2 and CYP3A4 Renal excretion: 50% Fecal excretion: 30% T 1/2: 8–12 h |
TBC differs between men and women: Men—36.7 L/h; Women—27 L/h | TBC differs by age at 39 years of age or older clearance is decreased by 0.219 L/h | ||
| Codeine | 1 |
Distribution: 7%–25% bound to serum proteins V d: 3–6 L/kg Metabolism: Liver, extensive by CYP2D6, CYP3A4 and UDP‐glucuronosyltransferases Renal excretion: 90% T 1/2: 3 h |
A specific CYP2D6 genotype are ultra‐rapid metabolizers (UM) of codeine who convert codeine into morphine, more rapidly and completely which may lead to higher than expected serum morphine levels, increasing the risk of overdose symptoms even at labeled doses | |||
| Colchicine | 1 |
F: approximately 45% Distribution: 39% bound to albumin V d: 5–8 L/kg Metabolism: Liver, partial via CYP3A and p‐glycoprotein substrate Renal clearance: 0.727 L/h/kg Renal excretion: 40%–65% Fecal excretion: extensive TBC: 30.3 L/h T 1/2: 26.6–31.2 |
In a single dose study, the plasma t 1/2 in elderly males was 30 and 34 h in elderly females | Following a single oral dose of colchicine 0.6 mg, the mean apparent t 1/2 was 24.92 ± 5.34 h for subjects age 18–30 years (n = 21) and 30.06 ± 10.78 h for subjects of mean age 62.83 years (n = 18) | ||
| Cyclobenzaprine | 2 | 2 |
F: 33%–55% Distribution: 93% bound to serum proteins Metabolism: Liver, extensive via P450 CYP3A4, CYP1A2, CYP2D6 Renal excretion: 51% TBC: 0.7 L/min T 1/2: 18 h |
In those >65 years of age receiving cyclobenzaprine hydrochloride extended release 30 mg capsules, the plasma t 1/2 was prolonged (50 h) compared to younger subjects (32 h) | ||
| Cyproheptadine | 2 | 3 |
Metabolism: Liver 57% Renal excretion: 40% Fecal excretion: 2%–20% T 1/2: 16 h |
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| Darifenacin | 3 |
F: 15%–25% Distribution: 98% bound to serum proteins, mostly alpha‐1‐acid glycoprotein V d: 163 L Metabolism: Liver, extensive via CYP3A, CYP2D6 Renal excretion: 60% Fecal excretion: 40% TBC: 32–40 L/h T 1/2: 13–19 h |
Total body clearance is 31.1% lower in females than males | Approximately 7% of Caucasians and 2% of African Americans are poor metabolizers (PM) of CYP2D6 metabolized drugs which shunts its metabolism to CYP3A4, C Max/AUC for oral darifenacin 15 mg once daily at steady state was 1.9 for PM and 1.7 for extensive metabolizers (EM) | ||
| Desipramine | 3 | 2 |
V d: 33–42 L/kg Metabolism: Liver, extensive Renal excretion: 70% T 1/2: 14.3–24.7 h |
Faster oral clearance in older men than older women | T 1/2 is prolonged in older adults (t 1/2 30 h) | "Slow" metabolizers have a t 1/2 77 h |
| Desloratadine | 1 |
Distribution: 82%–87% bound to serum proteins Metabolism: Liver, extensive via CYP2C8 Renal excretion: 40.6% Fecal excretion: 46.5% TBC: 150 L/h T 1/2: 19–40 h |
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| Diazepam | 1 |
F: ~98% Distribution: 95%–99.3% bound to serum proteins, CSF concentration is 1.6% of the total plasma concentration V d: 0.8–1 L/kg Metabolism: Liver, extensive Renal excretion:75% T 1/2: up to 48 h |
Protein binding is significantly greater in males than in females (1.87 L/kg in young females vs. 1.34 L/kg in young males) Greater clearance in women than men based on CYP3A4 clearance Shorter t 1/2 in men compared to women (32 h vs. 46.2 h) |
Protein binding is significantly greater in older females than younger females (2.46 L/kg in older females vs. 1.38 L/kg in younger females), the V d is larger for older males than younger males (1.65 L/kg for older males vs. 1.19 L/kg for younger males), t 1/2 increases by about 1 h for each year beginning with a t 1/2 of 20 h at 20 years, the mean t 1/2 increased with age to 79 h (range, 37–169 h) | ||
| Dicyclomine | 3 | 3 |
F: rapidly absorbed V d: 3.65 L/kg Metabolism: Liver, extensive via CYP3A Renal excretion: 79.5% Fecal excretion: 8.4% T 1/2: 1.8 h |
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| Digoxin | 1 |
F: 60%–80% Distribution: 25% bound to serum proteins, does cross the blood brain barrier V d: 475–500 L Metabolism: Liver 13%, substrate of p‐glycoprotein Renal excretion: 50%–70% Fecal excretion: 3%–5% T 1/2: 36–48 h |
Slower digoxin clearance in females | In the elderly, the V d may be reduced, which could increase serum concentrations, elimination may occur more slowly in older adults, due to age‐related decline in renal function | ||
| Dimenhydrinate | 3 |
F: well absorbed Metabolism: Liver, extensive |
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| Diphenhydramine | 3 | 3 |
F: 65%–100% Distribution: 76%–85% bound to serum proteins V d: 480–292 L/70 kg Metabolism: Liver 50% TBC: 11.7–49.2 ml/min/kg T 1/2: 4–8 h |
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| Doxepin | 3 |
Distribution: 80% bound to serum proteins V d: 11,930 L Metabolism: Liver, extensive via CYP2D6, CYP2C19 Renal Excretion: <3% T 1/2: 15.3 h |
Females had significantly higher dose‐corrected serum concentration doxepine/N‐doxepine (29%) | Patients older than 60 years had significantly higher dose corrected serum concentration of doxepin and N‐doxepin (48%), than patients up to 60 years | ||
| Doxylamine | 3 |
F: good T 1/2: 10.1–13.11 h |
T 1/2 in older men (mean age, 66 years) is 15.5 ± 2.1 h, in older women (mean age, 73 years), the t 1/2 was longer than in young women, but the difference was not statistically significant (12.2 h vs. 10.1 h) | |||
| Fentanyl | 1 |
Distribution: 80%–86% bound to serum proteins V d: 4–6 L/kg Renal excretion: <7% Fecal excretion: 1%–9% TBC: 42–53 L/h T 1/2: 3–27 h (depending on dosage form) |
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| Fesoterodine | 3 |
F: 52% Distribution: 50% bound to serum proteins V d: 169 L Metabolism: Liver, extensive via CYP2D6, CYP3A Renal excretion: 70% Fecal excretion: 7% |
In older adults, renal clearance of fesoterodine is reduced | |||
| Fluvoxamine | 1 |
F: 53% Distribution: 80% bound to serum proteins, mostly albumin V d: 25 L/kg Metabolism: Liver, extensive, Inhibitor of CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 Renal excretion: 94% Fecal excretion: 7% T 1/2: 15.6–16.3 h |
Higher serum concentration in women than men at 100 mg orally | In older patients the clearance of fluvoxamine was reduced by 50% | ||
| Furosemide | 1 |
F: 47%–70% Distribution: 91%–99% bound to serum proteins, mostly albumin V d: 0.2 L/kg Metabolism: Liver 10% Renal clearance: 2 ml/min/kg Renal excretion: 60%–90% Fecal excretion: 7%–9% TBC: 76 ml/min T 1/2: 30–120 min |
T 1/2 is prolonged in older adults | |||
| Haloperidol | 1 | 1 |
F: 60%–70% Distribution: >90% bound to serum proteins V d: 9.5–21.7 L/kg Metabolism: Liver, extensive via CYP3A Renal excretion: 33%–40% Fecal excretion: 15% |
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| Hydralazine | 1 |
F: 38%–50% Distribution: 88%–90% bound to serum proteins V d: 0.3–8.2 L/kg Metabolism: Liver, extensive Renal excretion: 3%–14% Fecal excretion: 3–12% T 1/2: 3–5 h |
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| Hydrocortisone | 1 |
F: 96% Distribution: 90% bound to serum proteins, mostly corticosteroid‐binding globuli V d: 34 L Metabolism: Liver, extensive via CYP3A Renal excretion: extensive TBC: 18 L/h T 1/2: 1–2 h |
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| Hydroxyzine | 3 | 3 |
V d: 16 L/kg Metabolism: Liver T 1/2: 3–20 h |
A mean t 1/2 of 29.3 h was reported after administration of 0.7 mg/kg hydroxyzine syrup to 9 healthy, fasting adults mean age 69.5 years | ||
| Hyoscyamine | 3 | 3 |
F: complete Renal excretion: majority unchanged T 1/2: 7.47 h |
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| Imipramine | 3 | 3 |
F: 94%–96% Distribution: 89% bound to serum proteins V d: 10–20 L/kg Metabolism: Liver, extensive via CYP2C19 T 1/2: 6–18 h |
In older adults t 1/2 ranges from 25–30 h | ||
| Isosorbide | 1 |
F: approximately 100% Distribution: <5%% bound to serum proteins V d: 0.6–0.7 L/kg Metabolism: Liver 98% Renal clearance: 371 ml/h Renal excretion: 93% Fecal excretion: 1% TBC: 115–140 ml/min T 1/2: 5 h |
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| Loperamide | 1 | 2 |
F: 0.3% Renal excretion: 1% Fecal excretion: 25%–40% T 1/2: 7–15 h |
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| Loratadine | 1 | 2 |
Distribution: 97% bound to serum proteins Metabolism: Liver, extensive via CYP3A, CYP2D6 T 1/2: 12–15 h |
Older adults (n = 12) reported to have a t 1/2 of 17.5 h (range of 11–38 h) | ||
| Loxapine | 2 |
F: complete Distribution: 96.6% bound to serum proteins Metabolism: Liver, extensive via CYP1A2, CYP3A4, CYP 2D6, p‐glycoprotein inhibitor T 1/2: 17.6 h |
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| Meperidine | 2 |
Distribution: 65%–80% bound to serum proteins, mostly albumin and alpha‐1‐acid glycoprotein V d: 3.1–5 L/kg Metabolism: Liver, extensive T 1/2: 3.2–3.7 h |
In older adults, meperidine is less protein bound; however, the clearance rate is unchanged, therefore the V d may be greater with more available free drug, and in older adults the t 1/2 is extended | |||
| Methocarbamol | 3 | 1 |
F: completely Metabolism: Liver, extensive Renal excretion: 10%–15% Fecal excretion: small amount T 1/2: 0.9–2 h |
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| Metho‐trimeprazine | 2 |
V d: 29.8 L/kg Metabolism: Liver Fecal excretion: small amount T 1/2: 15 h |
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| Metoprolol | 1 |
F: 50% Distribution: 10% bound to serum albumin, CSF concentration close to the plasma concentration V d: 3.2–5.6 L/kg Metabolism: Liver, extensive via CYP2D6 Renal excretion: 95% T 1/2: 3–4 h |
In CYP2D6 PM the mean t 1/2 of metoprolol is 7–9 h | |||
| Morphine | 1 |
F: 20%–40% Distribution: 20%–36% bound to serum proteins V d: 1–6 L/kg Metabolism: Liver Renal excretion: 90% Fecal excretion: 7–10% TBC: 20–30 ml/min/kg T 1/2: 1.5–4.5 h |
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| Nifedipine | 1 |
F: complete Distribution: 92%–98% bound to serum proteins Metabolism: Liver, extensive via CYP3A4 Renal excretion: 80% Fecal excretion: 20% TBC: 4.3 ml/min/kg T 1/2: 2 h |
Greater clearance in women, mainly due to CYP3A4 and is 20%–30% higher in young women than young men, women reach higher plasma levels at same dose | Clearance is significantly reduced in older subjects (unrelated to renal function) compared to younger subjects, following IV administration clearance in older subjects was 348 ml/min compared with 519 ml/min in young subjects | ||
| Nortriptyline | 3 | 2 |
F: 60% Distribution: 86%–95% bound to serum proteins V d: 15–27 L/kg Metabolism: Liver, extensive via CYP2D6 Renal excretion: 2% T 1/2: 15–39 h |
Plasma levels are mostly affected by CYP2D6 genotype and sex with females experiencing higher plasma levels | The t 1/2 may be >90 h in older adults | Nortriptyline plasma levels are mostly affected by CYP2D6 genotype and sex with females experiencing higher plasma levels |
| Olanzapine | 3 | 2 |
F: well absorbed Distribution: 93% bound to serum proteins, mostly albumin and alpha‐1‐acid glycoprotein V d: 1,000 L Metabolism: Liver, extensive via CYP1A2, CYP2D6 Renal excretion: 57% Fecal excretion: 30% TBC: 26.1 L/h T 1/2: 21–54 h |
Men from a population including individuals with Alzheimer's disease or schizophrenia cleared olanzapine 38% faster than women | The mean t 1/2 was 1.5 times greater in healthy patients aged ≥65 years compared with younger patients age <65 years, according to a study of 24 healthy subjects | |
| Orphenadrine | 3 |
F: 95% Renal excretion: 60% T 1/2: 13.2–20.1 h |
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| Oxcarbazepine | 2 |
Distribution: 40% bound to serum proteins V d: 49 L Metabolism: Liver, extensive Renal excretion: >95% Fecal excretion: <4% T 1/2: 2 h |
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| Oxybutynin | 3 | 3 |
F: 6% Distribution: >99% bound to serum proteins, mostly alpha‐1‐acid glycoprotein Metabolism: Liver, extensive via CYP3A4 Renal excretion: <0.1% T 1/2: 2–3 h |
Oxybutynin was not shown to have any differences in AUC and C Max for men or women | Oxybutynin follows the trend of increasing peak plasma levels and bioavailability with increasing age and frailty | |
| Paroxetine | 3 | 1 |
F: complete Distribution: 93%–95% bound to serum proteins Metabolism: Liver, extensive via CYP2D6, also an inhibitor of CYP2D6 Renal excretion: 64% Fecal excretion: 36% TBC: 76 ml/min T 1/2: 15–21 h |
Sex is correlated to paroxetine plasma concentration, estimates of V 2 in male subjects were 461.30 ± 259.75 and in female subjects were 346.41 ± 255.81 | A naturalized study of paroxetine showed a 2‐fold higher ratio of absolute serum concentration to dose adjusted serum concentrations in the oldest age group in comparison to controls <40 years of age | |
| Perphenazine | 3 | 3 |
F: 20% V d: 10–34 L/kg Metabolism: Liver, extensive via CYP2D6 Renal excretion: 80% TBC: 100 L/h T 1/2: 8.4–12.3 h |
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| Prednisone | 1 |
F: 92% Distribution: 70% bound to serum proteins, mostly albumin and corticosteroid‐binding globuli V d: 0.4–1 L/kg Metabolism: Liver, extensive T 1/2: 2–3 h |
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| Quetiapine | 3 | 1 |
F: 100% Distribution: 83% bound to serum proteins V d: 10 L/kg Metabolism: Liver, extensive via CYP3A4 Renal excretion: 73% Fecal excretion: 20% T 1/2: 6–7 h |
Sex was not shown to effect pharmacokinetics of quetiapine | In a pharmacokinetic study, quetiapine clearance was reduced by 40% in patients ≥65 years (n = 9) compared with young patients (n = 12) | |
| Quinidine | 1 |
F: 70%–80% Distribution: 80%–88% bound to serum proteins, mostly albumin and alpha‐1‐acid glycoprotein V d: 2–3 L/kg Metabolism: Liver, extensive via CYP3A4 Renal clearance: 1 ml/min/kg Renal excretion: 5%–20% Fecal excretion: 1%–3% TBC: 3–5 ml/min/kg T 1/2: 6–8 h |
Women clear quinidine at a faster rate than men and women have ECG changes in response to drug activity much quicker than men which is not explained by quinidine clearance | |||
| Ranitidine | 1 | 1 |
F: 50% Distribution: 15% bound to serum proteins V d: 1.04–4.09 L/kg Metabolism: Liver, minor Renal clearance: 24.6–31.8 L/h Renal excretion: 3%–70% Fecal excretion: 3.1 ml/min/kg TBC: 1.29–1.44 L/h/kg T 1/2: 1.9–3 h |
The t 1/2 is 3–4 h in older adults after oral administration likely due to a decrease in renal function | ||
| Risperidone | 1 | 1 |
F: 70% Distribution: 90% bound to serum proteins V d: 1–2 L/kg Metabolism: Liver, extensive via CYP 2D6 Renal clearance: 0.96 L/h Renal excretion: 70% Fecal excretion: 14% TBC: 3.2–13.7 L/h T 1/2: 3–20 h |
Sex‐related differences in risperidone metabolism are unlikely to be significant | When the plasma concentration was adjusted for subject body weight or maintenance dose there were still significant differences between groups with the oldest group having the highest adjusted concentration | Polymorphisms of CYP2D6 are more responsible for variation in risperidone metabolism than sex |
| Scopolamine | 3 |
Metabolism: extensive Renal excretion: <10% T 1/2: 9.5 h |
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| Solifenacin | 3 |
F: approximately 90% Distribution: 98% bound to plasma proteins, primarily alpha‐1‐acid glycoprotein V d: 599–671 L Metabolism: Liver, extensively via CYP3A4 Renal clearance: 0.67–0.76 L/h Renal excretion: 3%–6% Fecal excretion: 22.5% TBC: 9.4 L/h T 1/2: 40–68 h |
Solifenacin has a longer t 1/2 due to slower elimination and to longer time to reach C Max in older adults, this can be explained by the reduced absorption of solifenacin in older adults. Exposure to solifenacin is increased about 1.2‐fold in older subjects | |||
| Theophylline | 1 |
F: well absorbed Distribution: 40% bound to serum proteins V d: 450 ml/kg Metabolism: Liver, extensive via CYP1A2 Renal excretion: 10%–13% Fecal excretion: 7% TBC: 76 ml/min T 1/2: 8.7 h |
Protein binding is reduced in older adults, older adults had reduced clearance 0.59 ± 0.07 ml/kg/min, and increased mean t 1/2 of 9.8 h (1.6–18 h) this was in healthy older non‐smokers and was not significantly different from clearance values in otherwise healthy non‐smoking younger asthmatics | |||
| Thioridazine | 3 | 3 |
V d: 17.8 L/kg Metabolism: Liver, extensive Renal excretion: small amounts T 1/2: 21–24 h |
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| Tolterodine | 3 | 2 |
F: 77% V d: 113 L Metabolism: Liver, extensive via CYP2D6 Renal excretion: 77% Fecal excretion: 17% T 1/2: 1.9–3.7 h |
Metabolism is slowed in individuals who are CYP2D6 PM as metabolism is shunted to CYP3A4, t 1/2 is prolonged to 6.5 h with single doses and 9.6 h with multiple doses | ||
| Trazodone | 1 | 1 |
F: 65% Distribution: 89%–95% bound to serum proteins V d: 0.47–0.84 L/kg Metabolism: Liver, extensive Renal clearance: 3–5.3 L/h Renal excretion: 70%–75% Fecal excretion: 21% TBC: 5.3 L/h T 1/2: 7 h |
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| Triamterene | 1 |
F: 30%–70% Distribution: 55%–67% bound to serum proteins Metabolism: Liver 80% Renal excretion: 21% T 1/2: 1.5–2.5 h |
T 1/2 was 4.3 h in young adults, and was prolonged to 6.5 h in an older patient | |||
| Trifluoperazine | 3 | 3 |
F: readily absorbed Distribution: 90%–99% bound to serum proteins Metabolism: Liver T 1/2: 24 h |
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| Trospium | 3 |
F: 9.6% Distribution: 50%–85% bound to serum proteins V d: 395 L Metabolism: Liver Renal clearance: 29.07 L/h Renal excretion: 5.8% Fecal excretion: 85.2% T 1/2: 20 h |
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| Venlafaxine | 1 |
Distribution: 27%–30% bound to serum proteins V d: 7.5 L/kg Metabolism: Liver, extensive via CYP2D6 Renal clearance: 0.074–0.079 L/h/kg Renal excretion: 87% Fecal excretion: 2% TBC: 1.3 L/h/kg T 1/2: 5 h |
Venlafaxine serum concentrations differed in men and women with higher concentrations achieved by women (215 and 151 nmol/L), the ratio of absolute serum concentration in comparison to the dose‐adjusted serum concentration is 1‐ to 1.5‐fold higher in women than in men | The concentration to dose ratio of venlafaxine was 1.5‐fold higher in adults over 65 in comparison with controls <40 years old | The serum concentration of N‐desmethyl‐venlafaxine was 5.5‐fold higher in a subset of CYP2D6 PMs (p <.01) and 22‐fold higher in second subset of CYP2D6 PMs (p <.001) than in EM | |
| Warfarin | 1 |
F: completely absorbed Distribution: 99% bound to serum proteins V d: 0.14 L/kg Metabolism: Liver, extensive via CYP2C9, CYP2C19, CYP2C8, CYP2C18, CYP1A2, CYP3A4 Renal excretion: 92% TBC: dependent on CYP2C19 genotype T 1/2: 1 week |
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Abbreviations: ACB, Anticholinergic Cognitive Burden Scale; ADME, Absorption, Distribution, Metabolism and Excretion; ARS, Anticholinergic Risk Scale; AUC, area under the curve; CYP, cytochrome P450; F, Bioavailability; IV, intravenous; TBC, Total Body Clearance.