Buy Ventolin (Salbutamol) Inhaler Online

May 1, 2021

Drug Name: Ventolin / Salbutamol / Albuterol
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The price of Salbutamol may differ depending on the pharmacy and the region.
Some online pharmacies offer the option to purchase Ventolin without a prescription, with home delivery.
Before buying Ventolin, it’s essential to consult a healthcare professional to ensure it’s the appropriate treatment.
In USA, Ventolin is available in various forms, including inhalers and nebulizer solutions.

The studies reviewed were selected by WADA based on a combination of a literature search via PubMed and projects directly funded by WADA itself.

The methods used to measure and present results differed between studies: some researchers measured only the free (unchanged) form of the compound, while others assessed the levels of non-sulfated Ventolin in urine samples, including Ventolin released from glucuronide metabolites.

WADA requires systematic adjustment of urinary Ventolin concentrations when urine specific gravity (USG) exceeds 1.020, in order to determine an adverse analytical finding (AAF). This adjustment accounts for the hydration status of the individual at the time of urine collection. Across various studies, concentrations were reported both with and without USG correction, or in both formats.

The absorption of the portion swallowed after inhalation was characterized by the same oral bioavailability. Since pulmonary absorption of Ventolin is considered a rapid process, a zero-order absorption model was tested for inhalation. This model was retained even after integrating urinary data, with fixed parameters (F1, F2, ka1, ka2) to ensure accurate and realistic estimates of all other parameters.

One- and two-compartment distribution models were compared, evaluating clearance (CL) and central volume of distribution independently of the administration route.

Initially, concentrations of free and non-sulfated Ventolin in urine were modeled using a single compartment, with the same urinary excretion constant from plasma to urine (k34). Later, a model with separate compartments for each compound and distinct excretion constants was tested. Since data on urine volume was not available, a separate urine compartment was added, assuming constant urine production (UR_PROD). This compartment simulated natural urination, describing bladder filling and emptying. Predicted urinary Ventolin amounts were divided by the corresponding urine volume produced during the same period. It was assumed that the bladder was emptied before each Ventolin dose.

Several tests were performed to assess how USG correction influenced urinary concentrations (see Supplementary Material S1). Figure 2 illustrates the plasma and urinary concentration profiles of Ventolin over time used for the final model.

Overall, the combined data analysis (Supplementary Material S1) included 121 plasma concentration measurements (43 individual data points and 78 average profile points) and 796 urinary measurements (747 individual points and 49 average profile points). Median Ventolin doses per administration were 800 μg (ranging from 200 to 1600 μg) for inhalation and 8000 μg (ranging from 4000 to 12,000 μg) for oral administration. Daily doses ranged from 200 to 1600 μg (median 1600 μg) by inhalation, and from 4000 to 12,000 μg (median 8000 μg) orally.

Plasma concentrations of Ventolin were effectively modeled using a single-compartment approach with first-order absorption, applicable for both inhalation and oral administration. Adding interindividual variability (IIV) to any absorption or distribution parameters was not supported by the model, mainly due to the limited availability of plasma data. Parameter estimates are provided in Table S4.

Urinary Concentrations

Urinary concentration data were initially analyzed without differentiating between the various measured forms of Ventolin. The dataset combined both uncorrected concentrations and those adjusted for urine specific gravity (USG). Additionally, for both individual-level and study-level data, shared interindividual variability values were assigned to clearance (CL) and urinary production rate (UR_PROD). A proportional residual error model was applied to plasma data, while a combined error model better fit the urinary data (resulting in a decrease of the objective function value, ∆OFV = -49.1, compared to the proportional error model; p < 0.05).

Graphical analysis of urinary data showed no significant differences between non-sulfated Ventolin and its free form concentrations (Figure 2). Separating these two forms in the model did not improve estimation accuracy (Akaike Information Criterion difference ∆AIC = +15). The proportionality factor between excretion rates k35 and k34, when distinguishing between the two urinary Ventolin fractions (see Supplementary Material S1), was estimated at 0.001 with high uncertainty (relative standard error = 34,495%), indicating the model’s inability to distinguish between them. This aligns with previous studies showing negligible urinary concentrations of Ventolin glucuronide after both inhaled and oral administration. Therefore, the model was further developed without differentiating between the urinary fractions.

Visual inspection of the data showed no systematic differences between USG-corrected and uncorrected Ventolin concentrations (see Supplementary Material S5). Parameter estimates were similar in both cases, although variability in corrected UR_PROD was lower compared to uncorrected UR_PROD. As a result, model development continued using the combined dataset. The final baseline model’s parameter estimates are detailed in Supplementary Material S5.

The significant overlap observed in urinary pharmacokinetic profiles for various therapeutic doses (400 μg four times daily, 800 μg twice daily, or 2 mg once daily – Figure 4) highlights the difficulty in differentiating between legitimate therapeutic use and anti-doping rule violations. Urinary Ventolin concentrations exceeding 2000 ng/mL are primarily reached with oral doses of at least 4 mg per day.

This distinction becomes even more challenging due to variability in urinary concentrations under different conditions, as illustrated in Figure 5. Factors such as identical dosing, urination, or increased urine production lower urinary Ventolin levels, while physical activity tends to raise them. As expected, failing to correct for USG results in significantly higher predicted interindividual variability.

Lastly, Figure 6 shows that under a dosing regimen consistent with WADA’s 2017 recommendations (see Supplementary Material S1), 5.2% and 2.5% of measured urinary concentrations would exceed 1000 ng/mL and 1200 ng/mL, respectively, within two hours after administration. These findings support the reduction in the maximum daily dose introduced in WADA’s 2022 regulations. Some of the interindividual variability was explained by incorporating physical exercise as a binary covariate affecting the urinary production rate. However, the model did not account for exercise intensity, which might correlate more closely with urine production. Other factors—such as individual demographic characteristics, genetic polymorphisms, drug interactions, or inhalation techniques—could also contribute to the substantial variability seen in Ventolin distribution.

Considerations on Urinary Concentrations and Interpretation of Results

Given the high degree of interindividual variability (IIV) and residual error, measuring Ventolin concentration in a single urine sample collected at an unknown time after drug administration has limited value for determining an Adverse Analytical Finding (AAF). Nonetheless, even in a worst-case scenario where an individual takes 400 μg followed by 600 μg twice daily (the maximum dose allowed under WADA 2022 rules), the false-positive rate does not exceed 0.9%, a value considered acceptable.

The highest urinary concentrations are specifically associated with high oral doses of Ventolin. Therefore, a WADA Code violation can be strongly suspected when urinary Ventolin levels exceed 2000 ng/mL. However, there remains some uncertainty for concentrations near 1000 or 1200 ng/mL, as these could result either from permitted therapeutic use or misuse of the drug.

To further improve the ability to distinguish between permitted and prohibited use, it would be advisable to reduce the current maximum daily dose of 1600 μg. For example, limiting permissible dosing to 600 μg twice daily (b.i.d.) or 400 μg two or three times daily (b.i.d. or t.i.d.) would make it less likely for inhaled Ventolin concentrations to surpass WADA thresholds (T or DL). Additionally, such dosing regimens would align more closely with current medical recommendations than the existing higher limit.

It has been reported that maximum bronchodilation is achieved with a cumulative dose of 110 μg in healthy individuals. While higher doses may be necessary for asthmatic patients, excessive exposure to the drug—well beyond therapeutic levels—may have adverse effects and should not be recommended, even for athletes.

If detailed information is available regarding Ventolin administration (dose, timing) and urination frequency, our model can be used to predict the likelihood of exceeding WADA’s urinary concentration limits. This probability-based approach could assist WADA experts in identifying potential violations or clearing athletes by comparing their declared drug use with the urinary analysis results. However, in the context of anti-doping testing, the frequent absence of this critical information makes interpreting test results particularly challenging.

Since 2009, athletes with urinary Ventolin over the counter concentrations exceeding 1000 ng/mL have been able to demonstrate that these levels result from a dosing regimen within WADA limits by conducting a controlled excretion study. The results from such pharmacokinetic studies could be compared with prior predictions from our model, allowing for the calculation of maximum likelihood estimates of individual pharmacokinetic parameters using a Bayesian approach. Moreover, repeated measurements under controlled conditions may reduce the uncertainty of the athlete’s individual profile, helping to better distinguish between legitimate therapeutic use and potential Ventolin abuse.

Study Limitations

Several limitations of our study should be acknowledged. First, the limited plasma concentration data prevented us from estimating interindividual variability in absorption parameters, despite the known influence of factors like inhalation technique or medical conditions on Ventolin absorption. Second, variability in urinary production rate is likely underestimated by the model. https://fedeltahomecare.com