Actions of Detronin in details
The free base form of Detronin is pharmacologically equivalent to Detronin hydrochloride. Detronin acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors, resulting in relaxation of bladder smooth muscle. In patients with conditions characterized by involuntary detrusor contractions, cystometric studies have demonstrated that Detronin increases maximum urinary bladder capacity and increases the volume to first detrusor contraction.
Detronin is a racemic (50:50) mixture of R- and S-isomers. Antimuscarinic activity resides predominantly in the R-isomer. The active metabolite, N-desethyloxybutynin, has pharmacological activity on the human detrusor muscle that is similar to that of Detronin in in vitro studies.
How should I take Detronin?
It is very important that you use Detronin only as directed. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.
Detronin comes with a patient information insert. Read and follow the instructions in the insert carefully. Talk to your doctor if you have any questions.
Detronin is for use on the skin only. Do not get it in your eyes, nose, mouth, breasts, or genital area. Do not use it on skin areas that have cuts or scrapes. If it does get on these areas, rinse it off right away.
To use the gel:
- Wash your hands with soap and water before and after using Detronin.
- Before applying Detronin, wash the application site (eg, stomach, upper arms, shoulders, or thighs) with mild soap and water. Rinse well and pat dry.
- Tear and squeeze the entire contents of the packet into the palm of your hand or directly on the application site. Gently rub it until the gel dries.
- Do not apply Detronin on the same application site you applied the last one.
- Do not bathe, swim, shower, or exercise for 1 hour after applying Detronin.
- Cover the application site with a dry cloth after the medicine has dried to avoid direct contact or transfer of Detronin to another person.
To use the skin patch:
- Use Detronin exactly as directed by your doctor. It will work only if applied correctly.
- Wash your hands with soap and water before and after applying a patch. Do not touch your eyes until after you have washed your hands.
- Apply the patch right away after removing it from the protective pouch. Do not cut it into smaller pieces and do not touch the sticky surface of the patch.
- Apply the patch to a clean, dry, and intact skin area on your stomach, hips, or buttocks. Choose an area with little or no hair and free of scars, cuts, or irritation. Avoid putting the patch on areas where it could be rubbed off by tight clothing.
- Press the patch firmly in place with your fingertips to make sure that the edges of the patch stick well.
- When putting on each new patch, choose a different place within these areas. Do not put the new patch on the same place you wore the last one. Be sure to remove the old patch before applying a new one.
The gel form contains alcohol which is flammable. Do not use Detronin near heat, an open flame, or while smoking.
Dosing
The dose of Detronin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Detronin. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For bladder problems:
- For transdermal dosage form (gel):
- Adults—
- Anturol™: 84 milligrams (mg) or 3 pumps of gel applied on dry, intact skin once a day.
- Detronin®: Apply the gel on dry, intact skin once a day.
- Children—Use and dose must be determined by your doctor.
- Adults—
- For transdermal dosage form (skin patch):
- Adults—Apply one patch two times per week, which is one patch every 3 to 4 days.
- Children—Use and dose must be determined by your doctor.
- For transdermal dosage form (gel):
Missed Dose
If you forget to wear or change a patch, put one on as soon as you can. If it is almost time to put on your next patch, wait until then to apply a new patch and skip the one you missed. Do not apply extra patches to make up for a missed dose.
If you miss a dose of Detronin, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Ask your healthcare professional how you should dispose of any medicine you do not use.
After removing a used patch, fold the patch in half with the sticky sides together. Make sure to dispose of it out of the reach of children and pets.
Detronin administration
Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.
Wash your hands with soap and water before and after applying this medication. Also wash the skin area to be treated, using a mild soap or cleanser. Allow the skin to dry completely before applying Detronin topical.
Detronin topical can be applied to the skin on your stomach, upper arm, shoulder, or thigh.
Do not apply the gel to recently shaved skin, open wounds, scars, tattoos, or irritated or broken skin. Do not apply to the breasts or genital areas.
Apply the gel to a different place on any of these skin areas each time you use it. Do not apply the gel to the same skin two days in a row.
Each packet of Detronin Detronin gel is for one use only. Throw away the empty packet in a place where children and pets cannot get to it. Tear open the sealed packet and empty the entire contents into your hand. You may also empty the packet directly onto the treatment area.
To get the correct amount of Anturol gel for one application, press the pump down 3 times. You may pump the gel directly onto the treatment area.
Do not bathe, shower, swim, use a hot tub, or exercise vigorously for at least 1 hour after applying this medication.
It is best to cover treated skin areas with clothing after the gel has dried completely. This will help prevent getting this medicine on your other skin or on other people. If someone else does come into contact with a treated skin area, they should wash the contact area right away with soap and water.
Detronin gel is flammable. Avoid using near open flame, and do not smoke until the gel has completely dried on your skin.
Keep Detronin gel in its sealed packet until you are ready to use it. Store the packets at room temperature away from heat and moisture.
Detronin pharmacology
12.1 Mechanism of Action
The free base form of Detronin is pharmacologically equivalent to Detronin hydrochloride. Detronin acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors, resulting in relaxation of bladder smooth muscle. In patients with conditions characterized by involuntary detrusor contractions, cystometric studies have demonstrated that Detronin increases maximum urinary bladder capacity and increases the volume to first detrusor contraction.
Detronin is a racemic (50:50) mixture of R- and S-isomers. Antimuscarinic activity resides predominantly in the R-isomer. The active metabolite, N-desethyloxybutynin, has pharmacological activity on the human detrusor muscle that is similar to that of Detronin in in vitro studies.
12.3 Pharmacokinetics
Absorption
Detronin is transported across intact skin and into the systemic circulation by passive diffusion across the stratum corneum. The average daily dose of Detronin absorbed from the 39 cm2 Detronin system is 3.9 mg. The average (SD) nominal dose, 0.10 (0.02) mg Detronin per cm2 surface area, was obtained from analysis of residual Detronin content of systems worn over a continuous 4-day period during 303 separate occasions in 76 healthy volunteers. Following application of the first Detronin 3.9 mg/day system, Detronin plasma concentrations increase for approximately 24 to 48 hours, reaching average maximum concentrations of 3 to 4 ng/mL. Thereafter, steady concentrations are maintained for up to 96 hours. Absorption of Detronin is bioequivalent when Detronin is applied to the abdomen, buttocks, or hip. Average plasma concentrations measured during a randomized, crossover study of the three recommended application sites in 24 healthy men and women are shown in Figure 2.
Figure 2: Average plasma Detronin concentrations (Cp) in 24 healthy male and female volunteers during single-dose application of Detronin 3.9 mg/day to the abdomen, buttock, and hip (System removal at 96 hours).
Steady-state conditions are reached during the second Detronin application. Average steady-state plasma concentrations were 3.1 ng/mL for Detronin and 3.8 ng/mL for N-desethyloxybutynin (Figure 3). Table 3 provides a summary of pharmacokinetic parameters of Detronin in healthy volunteers after single and multiple applications of Detronin.
Figure 3: Average (SEM) steady-state Detronin and N-desethyloxybutynin plasma concentrations (Cp) measured in 13 healthy volunteers following the second transdermal system application in a multiple-dose, randomized, crossover study.
| Dosing | Detronin | |||
| Cmax (SD) (ng/mL) | Tmax ‡ (hr) | Cavg (SD) (ng/mL) | AUC (SD) (ng/mLxh) | |
| Single | 3.0 (0.8) | 48 | - | 245 (59)§ |
| 3.4 (1.1) | 36 | - | 279 (99)§ | |
| Multiple | 6.6 (2.4) | 10 | 4.2 (1.1) | 408 (108)¶ |
| 4.2 (1.0) | 28 | 3.1 (0.7) | 259 (57)#Þ | |
‡ Tmax given as median
§ AUCinf
¶ AUC0-96
#Þ AUC0-84
Distribution
Detronin is widely distributed in body tissues following systemic absorption. The volume of distribution was estimated to be 193 L after intravenous administration of 5 mg Detronin chloride.
Metabolism
Detronin is metabolized primarily by the cytochrome P450 enzyme systems, particularly CYP3A4, found mostly in the liver and gut wall. Metabolites include phenylcyclohexylglycolic acid, which is pharmacologically inactive, and N-desethyloxybutynin, which is pharmacologically active.
After oral administration of Detronin, pre-systemic first-pass metabolism results in an oral bioavailability of approximately 6% and higher plasma concentration of the N-desethyl metabolite compared to Detronin. The plasma concentration area under the time-concentration curve (AUC) ratio of N-desethyl metabolite to parent compound following a single 5 mg oral dose of Detronin chloride was 11.9:1.
Transdermal administration of Detronin bypasses first-pass gastrointestinal and hepatic metabolism, reducing the formation of the N-desethyl metabolite. Only small amounts of CYP3A4 are found in skin, limiting pre-systemic metabolism during transdermal absorption. The resulting plasma concentration AUC ratio of N-desethyl metabolite to parent compound following multiple Detronin applications was 1.3:1.
Figure 4: Average plasma concentrations (Cp) measured after a single, 96-hour application of the Detronin 3.9 mg/day system (AUCinf/96) and a single, 5 mg, oral immediate-release dose of Detronin chloride (AUCinf/8) in 16 healthy male and female volunteers.
Following intravenous administration, the elimination half-life of Detronin is approximately 2 hours. Following removal of Detronin, plasma concentrations of Detronin and N-desethyloxybutynin decline with an apparent half-life of approximately 7 to 8 hours.
Excretion
Detronin is extensively metabolized by the liver, with less than 0.1% of the administered dose excreted unchanged in the urine. Also, less than 0.1% of the administered dose is excreted as the metabolite N-desethyloxybutynin.
Specific Populations:
Renal Impairment: The effects of renal impairment on the pharmacokinetics of Detronin and N-desethyloxybutynin are not known.
Hepatic Impairment: The effects of hepatic impairment on the pharmacokinetics of Detronin and N-desethyloxybutynin are not known.
Geriatric: The pharmacokinetics of Detronin and N-desethyloxybutynin were similar in older and younger patients.
Pediatric: The pharmacokinetics of Detronin and N-desethyloxybutynin were not evaluated in individuals younger than 18 years of age.
Gender: There were no significant differences in the pharmacokinetics of Detronin in healthy male and female volunteers following application of Detronin.
Race: Available data suggest that there are no significant differences in the pharmacokinetics of Detronin based on race in healthy volunteers following administration of Detronin. Japanese volunteers demonstrated a somewhat lower metabolism of Detronin to N-desethyloxybutynin compared to Caucasian volunteers.
References
- DailyMed. "OXYBUTYNIN: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- EPA DSStox. "Oxybutynin: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Detronin are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Detronin. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
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Information checked by Dr. Sachin Kumar, MD Pharmacology
