Diclofenac potassium 12.5 mg liquid capsules: earlier and higher exposure to diclofenac. A fasted, single-dose, comparative, bioavailability study versus diclofenac potassium 12.5 mg tablets.

BACKGROUND: A fast-release liquid capsule formulation of low-dose diclofenac- K is available, which aims to improve patient convenience and compliance. The new formulation is a soft gelatin capsule designed to facilitate faster absorption of diclofenac versus the tablet form with anticipated overall comparable bioavailability. OBJECTIVES: To compare the bioavailability of diclofenac-K 2 × 12.5 mg liquid capsules versus diclofenac- K 2 × 12.5 mg tablets. DESIGN: This randomized, open-label crossover, single-dose study was conducted in 42 healthy subjects (mean age 23.5 years) given diclofenac-K 2 × 12.5 mg liquid capsules or tablets over two 1-day treatment periods separated by a 14-day washout period. RESULTS: Diclofenac-K 12.5 mg liquid capsules were equivalent to the tablets in terms of total systemic exposure (mean AUCt ratio = 112%, 2-sided 90% CI = (107%, 116%)). However, the mean Cmax for the liquid capsules (1,090 ng/ml) was almost double that of the tablets (583 ng/ml) (mean Cmax ratio = 196%, 2-sided 90% CI = (169%, 227%)). Median tmax was ~ 10 min faster with the liquid capsules (0.42 h) compared with the tablets (0.58 h) and AUCtmax ref for the liquid capsules (294 ng×h/ml) was almost double the value for the tablets (158 ng×h/ml). This indicated a faster absorption of diclofenac from the liquid capsules compared to the tablet. There were no differences between the two treatments regarding safety, and both drugs were well tolerated. CONCLUSIONS: This study demonstrated equivalent overall systemic exposure to diclofenac but a faster absorption and substantially greater early exposure to diclofenac from diclofenac-K liquid capsules compared with the tablets, which may lead to a more rapid analgesic effect in patients.

Systemic bioavailability of topical diclofenac sodium gel 1% versus oral diclofenac sodium in healthy volunteers.

Systemic bioavailability and pharmacodynamics of topical diclofenac sodium gel 1% were compared with those of oral diclofenac sodium 50-mg tablets. In a randomized, 3-way crossover study, healthy volunteers (n = 40) received three 7-day diclofenac regimens: (A) 16 g gel applied as 4 g to 1 knee 4 times daily (4 g on surface area 400 cm(2)), (B) 48 g gel applied as 4 g per knee 4 times daily to 2 knees plus 2 g gel per hand applied 4 times daily to 2 hands (12 g on 1200 cm(2)), and (C) 150 mg oral diclofenac applied as 50-mg tablets 3 times daily. Thirty-nine participants completed all 3 regimens. Systemic exposure was greater with oral diclofenac (AUC(0-24), 3890 +/- 1710 ng x h/mL) than with topical treatments A (AUC(0-24), 233 +/- 128 ng x h/mL) and B (AUC(0-24), 807 +/- 478 ng x h/mL). Oral diclofenac inhibited platelet aggregation, cyclooxygenase-1 (COX-1), and COX-2. Topical diclofenac did not inhibit platelet aggregation and inhibited COX-1 and COX-2 less than oral diclofenac. Treatment-related adverse events were mild and limited to application site reactions with diclofenac sodium gel 1% (n = 4) and gastrointestinal reactions with oral diclofenac (n = 3). Systemic exposure with diclofenac sodium gel 1% was 5- to 17-fold lower than with oral diclofenac. Systemic effects with topical diclofenac were less pronounced.

Novel, single-dose, topical treatment of tinea pedis using terbinafine: results of a dose-finding clinical trial.

Tinea pedis is the most common dermatophytosis requiring topical antifungals for at least 1-4 weeks. To determine the effectiveness of a novel topical single dose formulation of terbinafine (film forming solution-FFS) in the treatment of tinea pedis, 344 outpatients from 43 dermatological centres in France and Bulgaria suffering from tinea pedis with possible extension to soles confirmed by mycological examination (direct and culture) were evaluated for efficacy of terbinafine 1%, 5%, 10% FFS in a randomised double blind vehicle controlled parallel group dose finding study. Evaluations were carried out at baseline, 1 and 6 weeks after a single application of FFS. Effective treatment rate based on negative mycology (direct and culture) and minimal signs and symptoms (two or less with only mild recorded) was measured at week 6. Effective treatment rates at week 6 with terbinafine 1%, 5% and 10% FFS were 66%, 70%, 61% compared with 18% with placebo. All three active preparations were shown to be significantly superior to placebo (P < 0.001). Terbinafine 1% and 5% FFS were shown to be non-inferior to terbinafine 10% FFS. Terbinafine 1% FFS is an effective, safe dose for the treatment of tinea pedis. This novel product represents a significant advance with the enhanced compliance and convenience that it offers.

Pharmacokinetics, safety and efficacy from randomized controlled trials of 1 and 2 mg nicotine bitartrate lozenges (Nicotinell).

BACKGROUND: The use of nicotine replacement therapy (NRT) can almost double the chances of success for smokers to quit. Nevertheless, there is still a considerable number of cessation attempts that are made without any treatment. This novel oral formulation, (lozenge containing nicotine bitartrate dihydrate) has been developed to enlarge the offer for efficient smoking cessation drug therapies, assuming that increasing treatment options will bring more smokers to find the support they personally need to stop smoking. METHODS: Three pharmacokinetic (PK), one safety and two efficacy studies were carried out with Nicotinell lozenges. PK trials were: (1) a single-dose, three-way crossover study comparing 1 and 2 mg lozenges with 2 mg nicotine gum; (2) a multiple-dose, two-way crossover study comparing 1 mg lozenge with 2 mg gum; (3) a multiple-dose, three-way crossover study comparing 1 and 2 mg lozenges with 4 mg gum. Safety trial: (4) a single dose study to assess the safety of swallowing up to 12 lozenges containing 1 mg nicotine. Efficacy trials: two efficacy studies in (5) France and (6) the USA, including more than 900 smokers followed-up for up to one year, conducted with the 1 mg lozenge. RESULTS: The results of the individual PK trials showed that the 1 mg Nicotinell lozenge is bioequivalent to 2 mg polacrilex gum, as demonstrated by similar blood PK parameters (tmax, Cmax, AUC). The 2 mg lozenge was found to deliver quantities of nicotine that were intermediate between those delivered by 2 and 4 mg polacrilex gum. The short-term efficacy of the 1 mg lozenge in comparison with placebo was also demonstrated with significantly more subjects continuously abstinent from smoking with active lozenges on week 6 in two different populations: moderate to heavy smokers (FTND between 4 and 7) OR = 1.72 [95% CI: 1.05-2.80]; heavy to very heavy smokers (FTND 6 and over) OR = 2.87 [95% CI: 1.18-6.97]. Nicotinell lozenges were found to be safe with mainly mild and reversible adverse events. The safety of the 1 mg lozenge formulation, even when misused was also demonstrated. CONCLUSION: The data presented in this review demonstrate high nicotine bioavailability, excellent safety profile and proven short-term efficacy of Nicotinell lozenges. At nominal equivalent doses 1 and 2 mg Nicotinell lozenges were shown to deliver larger amounts of bioavailable nicotine compared to the nicotine polacrilex gum. According to the data developed here, the systemic exposure to nicotine could be ranked: 4 mg polacrilex gum > 2 mg Nicotinell lozenge > 1 mg Nicotinell lozenge = 2 mg polacrilex gum.Adverse events observed during the clinical trials were mild or moderate in severity, transient and completely reversible. With respect to efficacy in smoking cessation, significantly higher continuous abstinence rates were achieved with lozenge compared to placebo. In conclusion, Nicotinell lozenges offer a valuable addition to the therapeutic armamentarium available for smoking cessation.

The efficacy and safety of low-dose diclofenac sodium 0.1% gel for the symptomatic relief of pain and erythema associated with superficial natural sunburn.

A randomised, double-blind, single-centre, vehicle-controlled clinical trial was conducted to assess the efficacy and tolerability of diclofenac-Na 0.1% gel in 172 subjects suffering from acute first-degree natural sunburn. Overall 172 subjects with skin phototypes II-IV were randomised in a ratio of 2:1 to receive two applications of either diclofenac-Na 0.1% Emulgel gel or its vehicle Emulgel gel, 6 and 10 hours after the end of sun exposure. Subjects were drawn from a target population of healthy volunteers and well outdoor sunbathers with normal tolerance to ultraviolet light and the sun. Previously untanned areas were exposed to carefully determined standardised doses of sun (2.8 individual minimal erythema doses) on 15% body surface area to induce first-degree sunburn. After administration of diclofenac-Na 0.1% gel, subjects reported a significant reduction in spontaneous pain intensity compared with those on vehicle. Pain relief was rapid with a reduction in erythema, which was apparent within the first few hours after the first application of the trial medication with a maximum effect observed up to 30 hours after sun exposure. A good', very good', or excellent' cooling effect was recorded by 85% of subjects after treatment. Reported treatment-emergent adverse effects were infrequent, generally mild and none were considered to be related to the trial medication. Only one severe treatment emergent adverse event (abdominal pain) was recorded in the active group, and another (burning sensation) with vehicle.