Testotop Gel - Manufacturer says 10min soaking time is sufficient?

[Mr Muc.]

Hello everyone and thanks for this great forum!
I have already been able to extract many tips.

With regard to application, however, I still have one point which, according to the manufacturer's application instructions, contradicts the other tips. Here, 10 minutes application time is described as sufficient...?!


>>
Prescribing Info:
You must use the gel as prescribed by your doctor.
If you normally bathe in the morning, shower or wash in the morning, apply Testotop Gel 125 mg at least 10 minutes before bathing, showering or washing.

....
The other ingredients are:
Ethanol 96 %, carbomer 980, propylene glycol, trometamol,
sodium edetate (Ph.Eur.) and purified water.

<<

Testotop also "advertises" that this is a difference to Androgel/Testogel.

Can that really be???

 

[sammmy]

Androgel says not to wash off the gel for at least 2 hours. Showering at 2 hours results in 13% decrease of the average testosterone concentration in blood.

Testotop is a different formulation so follow the manufacturer notes - presumably they made studies. Probably it drives the testosterone faster into the skin so you can wash off the remainder on top of skin faster.

 

[Mr Muc.]

@sammy

Thx a lot! Sounds to good to be true. So testotop would be the „perfect“ gel?
Hard to believe it‘ sooo much better and easier in the daily usage…

 

[sammmy]

Galen, the manufacturer of Testotop seems to be more concerned with transmitting the testosterone to children and women than with absorption.

I doubt it reaches near maximum absorption at 10 minutes because the formulation is not drastically different than Androgel but Testotop compensates by providing more testosterone per dose and a higher concentration of 2.5% so it drives more testosterone in the skin than Androgel at 10 mins: the recommended starting dose for Testotop is 125mg testosterone, while it is 40.5mg testosterone for Androgel. Clearly Androgel must have more optimized delivery method (waiting 2 hours instead of 10 mins before washing off) that is wasting less testosterone.

The bottom line is that Testotop washed at 10 mins should provide similar concentration as Androgel washed off at 2 hours because Testotop has more testosterone per dose and more of it is wasted after washing off. Keeping Testotop longer than 10 mins on skin will probably provide higher levels of testosterone.

 

[madman]

Hello everyone and thanks for this great forum!
I have already been able to extract many tips.

With regard to application, however, I still have one point which, according to the manufacturer's application instructions, contradicts the other tips. Here, 10 minutes application time is described as sufficient...?!


>>
Prescribing Info:
You must use the gel as prescribed by your doctor.
If you normally bathe in the morning, shower or wash in the morning, apply Testotop Gel 125 mg at least 10 minutes before bathing, showering or washing.

....
The other ingredients are:
Ethanol 96 %, carbomer 980, propylene glycol, trometamol,
sodium edetate (Ph.Eur.) and purified water.

<<

Testotop also "advertises" that this is a difference to Androgel/Testogel.

Can that really be???

The manufacturers of the various transdermal T-gel products recommend longer wait times of 2-5 hrs due to decreased bioavailability of testosterone and erring on the side of caution when it comes to side effects from transference to others (prepubertal children/women).

Most T gel preparations are formulated as a hydroalcoholic gel, other preparations use other enhancers in lotions.

Skin structural differences may be one of the reasons for significant variations in the bioavailability of the drug.

Look over the formulations of Androgel vs Testotop let alone many others.

What is the key inactive ingredient?

Clear as day.




Androgel

*Pharmacologically inactive ingredients in AndroGel 1% are carbomer 980, ETHANOL 67.0%, isopropyl myristate, purified water, and sodium hydroxide. These ingredients are not pharmacologically active



Table 11.1 Advantages and disadvantages of transdermal testosterone for replacement in hypogonadal men

Table 11.2 Characteristics of some testosterone gels (based on manufacturer’s label)

Androgel

*Pharmacologically inactive ingredients in AndroGel 1% are carbomer 980, ethanol 67.0%, isopropyl myristate, purified water, and sodium hydroxide. These ingredients are not pharmacologically active




Androgel leaflet

5.2 Potential for Secondary Exposure to Testosterone

Cases of secondary exposure resulting in the virilization of children have been reported in postmarketing surveillance. Signs and symptoms have included enlargement of the penis or clitoris, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases, these signs and symptoms regressed with the removal of the exposure to testosterone gel. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. The risk of transfer was increased in some of these cases by not adhering to precautions for the appropriate use of the topical testosterone product. Children and women should avoid contact with unwashed or unclothed application sites in men using AndroGel 1% [see Dosage andAdministration (2.2), Use in Specific Populations (8.1) and Clinical Pharmacology (12.3)].

Inappropriate changes in genital size or development of pubic hair or libido in children, changes in body hair distribution, a significant increase in acne, or other signs of virilization in adult women should be brought to the attention of a physician and the possibility of secondary exposure to testosterone gel should also be brought to the attention of a physician. Testosterone gel should be promptly discontinued until the cause of virilization has been identified.




Secondary Exposure to Testosterone in Children

Cases of secondary exposure to testosterone resulting in the virilization of children have been reported in postmarket surveillance. Signs and symptoms of these reported cases have included enlargement of the clitoris (with surgical intervention) or the penis, development of pubic hair, increased erections and libido, aggressive behavior, and advanced bone age. In most cases with a reported outcome, these signs and symptoms were reported to have regressed with the removal of the testosterone gel exposure. In a few cases, however, enlarged genitalia did not fully return to age-appropriate normal size, and bone age remained modestly greater than chronological age. In some of the cases, direct contact with the sites of application on the skin of men using testosterone gel was reported. In at least one reported case, the reporter considered the possibility of secondary exposure from items such as the testosterone gel user's shirts and/or other fabric, such as towels and sheets [see Warnings and Precautions (5.2)].




11 DESCRIPTION

AndroGel (testosterone gel) 1% is a clear, colorless hydroalcoholic gel containing testosterone.

The active pharmacologic ingredient in AndroGel 1% is testosterone, an androgen. TestosteroneUSP is a white to practically white crystalline powder chemically described as 17-betahydroxyandrost-4-en-3-one. The structural formula is:

Pharmacologically inactive ingredients in AndroGel 1% are carbomer 980, ethanol 67.0%, isopropyl myristate, purified water, and sodium hydroxide. These ingredients are not pharmacologically active




12.3 Pharmacokinetics

Absorption

AndroGel 1% delivers physiologic amounts of testosterone, producing circulating testosterone concentrations that approximate normal concentrations (298 - 1043 ng/dL) seen in healthy men.AndroGel 1% provides continuous transdermal delivery of testosterone for 24 hours following a single application to intact, clean, dry skin of the shoulders, upper arms, and/or abdomen.

AndroGel 1% is a hydroalcoholic formulation that dries quickly when applied to the skin surface. The skin serves as a reservoir for the sustained release of testosterone into the systemic circulation. Approximately 10% of the testosterone dose applied on the skin surface from AndroGel is absorbed into the systemic circulation. In a study with AndroGel 1% 100 mg, all patients showed an increase in serum testosterone within 30 minutes, and eight of nine patients had a serum testosterone concentration within the normal range by 4 hours after the initial application. Absorption of testosterone into the blood continues for the entire 24-hour dosing interval. Serum concentrations approximate the steady-state concentration by the end of the first 24 hours and are at a steady state by the second or third day of dosing.

With single daily applications of AndroGel 1%, follow-up measurements 30, 90, and 180 days after starting treatment have confirmed that serum testosterone concentrations are generally maintained within the eugonadal range. Figure 1 summarizes the 24-hour pharmacokinetic profiles of testosterone for hypogonadal men (less than 300 ng/dL) maintained on AndroGel 1% 50 mg or 100 mg for 30 days. The average (± SD) daily testosterone concentration produced byAndroGel 1% 100 mg on Day 30 was 792 (± 294) ng/dL and by AndroGel 1% 50 mg 566 (±262) ng/dL.








A study from 2002 using 2 doses of a transdermal testosterone gel (Testotop®)




Pharmacokinetics of a new transdermal testosterone gel in gonadotrophin-suppressed normal men (2002)
C Rolf, S Kemper, G Lemmnitz1, U Eickenberg2 and E Nieschlag


Abstract

Objective: In a phase I single-center, open, randomized study, the pharmacokinetics of two doses of a transdermal testosterone gel containing 2.5% testosterone were evaluated in 26 healthy male volunteers.

Design: To eliminate the influence of endogenous serum testosterone, gonadotrophins, and endogenous testosterone secretion were suppressed by a single intramuscular injection of 400 mg norethisterone enanthate. Fourteen men applied 5.0 g and 12 men applied 2.5 g testosterone gel daily for 10 days. Half the men in each group washed the gel off 10 min after it had been applied.

Results: In all the men, a marked suppression of LH, FSH, testosterone, dihydrotestosterone (DHT), and estradiol was observed after norethisterone treatment. Physiological serum concentrations of testosterone were restored during the 10-day treatment period in the group of men applying 5.0 g testosterone gel. Increasing serum concentrations of testosterone from day 1 to day 10 were observed. Oestradiol and DHT concentrations did not exceed normal values. Washing 10 min after gel application did not influence the resorption of testosterone. A dose of 2.5 g testosterone gel was insufficient to achieve physiological serum concentrations of testosterone.

Conclusion: Testosterone replacement treatment with 5.0 g of this 2.5% testosterone gel is able to achieve constant physiological testosterone concentrations in gonadotrophin-suppressed men. Washing the skin after 10 min does not influence the pharmacokinetic profile and thus significantly reduces the risk of contamination of female partners or infants.




Recently, the first testosterone-containing transdermal gel (AndroGel) has been approved by the Food and Drugs Administration in the USA. Testosterone gel replacement improves sexual function and mood, increases lean body mass and bone density, in addition to muscle strength (principally in the legs), and decreases fat mass in hypogonadal men, with less skin irritation and discontinuation rates compared with the permeation-enhanced Androderm patch (9, 10). This gel is well received in the USA. We were therefore encouraged to investigate further another transdermal testosterone gel which was developed at approximately the same time in Germany.




Materials and methods

Participants

The drug under investigation was a hydroalcoholic gel containing 2.5% testosterone. When it was applied to the skin, the solvent evaporated quickly, without any perceptible residue. The men were allocated to two groups: group I received a dose of 5 g testosterone gel daily for 10 days (n = 14); Group II received 2.5 g gel daily for 10 days (n = 12): The gel was applied in the morning at approximately 0800 h. Volunteers were instructed to apply the gel on their abdomen over as large an area as possible. After 10 min, when the alcohol had evaporated, half the volunteers in each group (groups Ia and IIa, respectively) washed their abdomen with water and soap and dried their skin thoroughly, where the gel had been applied.

A final examination was performed on study day 13and a follow-up evaluation took place on study day 19. If any test revealed a clinically significant abnormality, additional blood samples were obtained on day 41.




Results

Pharmacokinetics

Five days after injection of norethisterone enanthate, pronounced suppression of FSH and LH, and correspondingly of testosterone, was achieved in all the men. Diurnal variation of testosterone secretion disappeared completely (Fig. 1).

Washing of the skin 10 min after gel application was without influence on transdermal testosterone absorption (Table 1; Fig. 1). On day 1 after the first gel application, serum testosterone increased relatively rapidly, reaching a plateau after approximately 4 h and remaining greater than baseline for the remainder of the study day (Fig. 1). In all groups on the first day of gel application, physiological testosterone concentrations were observed only for a relatively short time or were not attained at all. However, during prolonged treatment, an increase in serum testosterone was observed on the following study days.




Discussion

During the study, an increase in serum testosterone concentrations from day 1 to day 10 was observed.According to the hyperbolic kinetic model, which best fitted the data, no further significant accumulations should be expected. Recently, with the transdermal testosterone gel AndroGel (containing 1% testosterone), comparable accumulation during the first study days was reported (9). With 10 g AndroGel containing 100 mg testosterone, maximal serum concentrations (mean ± S.E.M.) of testosterone 29.1 ± 4 .0 nmol/l after 1 day and 46.3 ± 5:6 nmol/l after 7 days were achieved. In the present study after the application of 5.0 g testosterone gel, slightly lower serum concentrations of testosterone were found, despite the application of a greater absolute dose of testosterone (125 mg/day). However, serum testosterone concentrations in the normal range are the aim of androgen replacement therapy(4), and with 5.0 g testosterone, we achieved average serum concentrations of testosterone above this range. In group I, four men, two from each subgroup, did not achieve average serum concentrations of testosterone in the normal range.

Washing the skin with soap and water did not have an adverse influence on the absorption of testosterone into the skin, as comparable pharmacokinetic profiles were observed in the groups of patients who did or did not wash the skin 10 min after gel application. A similar observation has meanwhile been reported by Bae et al. (16), in a study in which men washed the skin 1 h after AndroGel application, with no influence on serum testosterone concentrations.

Topical application of androgens without protection may cause side effects in other people through contamination, especially in prepubertal children and in women (17). These side effects may be largely irreversible when androgen treatment is discontinued (18). To achieve good resorption of testosterone during AndroGel treatment, patients are instructed not to wash the skin for 5 –6 h; in addition, it has been shown that a significant increase in serum concentrations of testosterone could be observed in women after skin contact with men who had applied AndroGel several hours earlier (19). The rapid absorption of the testosterone from the gel used in the present study offers the possibility of washing the skin immediately after the alcohol has evaporated, thus significantly reducing the risk of contamination of other persons.

In our study, body mass index, and thus probably subcutaneous adipose tissue content, had no influence on serum concentrations of testosterone (data not shown). We cannot exclude that the area of application and the technique of gel application, which vary between individuals, influence the resorption of testosterone, although we found no evidence for this. However, in the normal patient population, even larger variations in technique and area of application must be expected. Therefore, to mimic this situation, we did not dictate the application area.




Conclusions

Daily testosterone replacement therapy with 5.0 g of the 2.5% testosterone gel is able to achieve constant physiological testosterone concentrations in gonadotrophin-suppressed men. Washing the skin after 10 min does not have an adverse influence on the pharmacokinetic profile, thus significantly reducing the risk of contamination of female partners, or infants. Testosterone gel treatment appears to be superior to the conventional administration of testosterone esters, orally or by injection because a physiological circadian profile can be achieved, but it is also superior to transdermal patches, as the gel leaves no visible sign after application.








Some key points to keep in mind:

*Washing the skin with soap and water did not have an adverse influence on the absorption of testosterone into the skin, as comparable pharmacokinetic profiles were observed in the groups of patients who did or did not wash the skin 10 min after gel application. A similar observation has meanwhile been reported by Bae et al. (16), in a study in which men washed the skin 1 h after AndroGel application, with no influence on serum testosterone concentrations


*Topical application of androgens without protection may cause side effects in other people through contamination, especially in prepubertal children and in women (17). These side effects may be largely irreversible when androgen treatment is discontinued (18). To achieve good resorption of testosterone during AndroGel treatment, patients are instructed not to wash the skin for 5 –6 h; in addition, it has been shown that a significant increase in serum concentrations of testosterone could be observed in women after skin contact with men who had applied AndroGel several hours earlier (19). The rapid absorption of the testosterone from the gel used in the present study offers the POSSIBILITY of washing the skin immediately after the alcohol has evaporated, thus significantly reducing the risk of contamination of other persons.


*With 10 g AndroGel containing 100 mg testosterone, maximal serum concentrations (mean ± S.E.M.) of testosterone 29.1 ± 4 .0 nmol/l after 1 day and 46.3 ± 5:6 nmol/l after 7 days were achieved. In the present study after the application of 5.0 g testosterone gel, SLIGHTLY LOWER serum concentrations of testosterone were found, despite the application of a greater ABSOLUTE DOSE of testosterone (125 mg/day). However, serum testosterone concentrations in the normal range are the aim of androgen replacement therapy(4), and with 5.0 g testosterone, we achieved average serum concentrations of testosterone above this range. In group I, four men, two from each subgroup, did not achieve average serum concentrations of testosterone in the normal range.