Comparison of Pharmacokinetics of Vardenafil Administered Using an Ultrasonic Nebulizer for Inhalation vs a Single 10-mg Oral Tablet.

INTRODUCTION: Delivery of vardenafil (for improvement of erectile function) via the inhaled route of administration may be advantageous in that this avoids extensive first pass metabolism and may therefore increase the bioavailability (hence the reliability of absorption) and shorten the time of pharmacological onset of activity. A unique nebulizer design has been developed by the sponsor (Advanced Medical Institute Pty Ltd) that is capable of delivering relatively large volumes of drug. AIM: The primary objective of the Phase 1 study was to assess and compare the pharmacokinetics of a single dose of vardenafil 10-mg tablet and a single dose of vardenafil solution administered via inhalation using an ultrasonic nebulizer device. Secondary objective was to assess the safety of vardenafil administered via inhalation using an ultrasonic nebuliser device. METHODS: Two-part study in healthy volunteers. Dose-ranging study was performed in two subjects to determine the appropriate inhalational dose, followed by an open, randomized, crossover, single dose pharmacokinetic study in 12 subjects, which compared a single 10-mg oral dose to the inhalation dose. MAIN OUTCOME MEASURES: Cmax, Cmax/Dose, Tmax, ke, t1/2, AUC0-t, AUCt-∞, AUC0-∞, AUC0-∞, AUC0-∞/Dose, and % area extrapolated. RESULTS: The two treatments are not bioequivalent, with vardenafil absorbed and eliminated faster and with less variability using the nebulizer for drug delivery. Administration via the inhalational route was not associated with any clinically significant changes in blood pressure or heart rate, and no serious adverse events were recorded, demonstrating an acceptable safety profile. CONCLUSION: To our knowledge, this is the first report of the administration of vardenafil HCl via the pulmonary route of administration. This trial demonstrates that vardenafil HCl may be administered using the ultrasonic nebulizer to reach blood levels comparable with those produced by a vardenafil 10-mg oral tablet, faster and using less drug. This new route of administration may potentially improve the onset of action, reliability, and safety for this class of drug.

An ex vivo, assessor blind, randomised, parallel group, comparative efficacy trial of the ovicidal activity of three pediculicides after a single application--melaleuca oil and lavender oil, eucalyptus oil and lemon tea tree oil, and a "suffocation" pediculicide.

BACKGROUND: There are two components to the clinical efficacy of pediculicides: (i) efficacy against the crawling-stages (lousicidal efficacy); and (ii) efficacy against the eggs (ovicidal efficacy). Lousicidal efficacy and ovicidal efficacy are confounded in clinical trials. Here we report on a trial that was specially designed to rank the clinical ovicidal efficacy of pediculicides. Eggs were collected, pre-treatment and post-treatment, from subjects with different types of hair, different coloured hair and hair of different length. METHOD: Subjects with at least 20 live eggs of Pediculus capitis (head lice) were randomised to one of three treatment-groups: a melaleuca oil (commonly called tea tree oil) and lavender oil pediculicide (TTO/LO); a eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO); or a "suffocation" pediculicide. Pre-treatment: 10 to 22 live eggs were taken from the head by cutting the single hair with the live egg attached, before the treatment (total of 1,062 eggs). TREATMENT: The subjects then received a single treatment of one of the three pediculicides, according to the manufacturers' instructions. Post-treatment: 10 to 41 treated live eggs were taken from the head by cutting the single hair with the egg attached (total of 1,183 eggs). Eggs were incubated for 14 days. The proportion of eggs that had hatched after 14 days in the pre-treatment group was compared with the proportion of eggs that hatched in the post-treatment group. The primary outcome measure was % ovicidal efficacy for each of the three pediculicides. RESULTS: 722 subjects were examined for the presence of eggs of head lice. 92 of these subjects were recruited and randomly assigned to: the "suffocation" pediculicide (n = 31); the melaleuca oil and lavender oil pediculicide (n = 31); and the eucalyptus oil and lemon tea tree oil pediculicide (n = 30 subjects). The group treated with eucalyptus oil and lemon tea tree oil had an ovicidal efficacy of 3.3% (SD 16%) whereas the group treated with melaleuca oil and lavender oil had an ovicidal efficacy of 44.4% (SD 23%) and the group treated with the "suffocation" pediculicide had an ovicidal efficacy of 68.3% (SD 38%). CONCLUSION: Ovicidal efficacy varied substantially among treatments, from 3.3% to 68.3%. The "suffocation" pediculicide and the melaleuca oil and lavender oil pediculicide (TTO/LO) were significantly more ovicidal than eucalyptus oil and lemon tea tree oil pediculicide (EO/LTTO) (P < 0.0001). Ranking: 1. "Suffocation" pediculicide (68.3% efficacy against eggs); 2. Melaleuca oil and lavender oil (44.4%) pediculicide; 3. Eucalyptus oil and lemon tea tree oil (3.3%) pediculicide. The "suffocation" pediculicide and TTO/LO are also highly efficacious against the crawling-stages. Thus, the "suffocation" pediculicide and TTO/LO should be recommended as first line treatments.

A randomised, assessor blind, parallel group comparative efficacy trial of three products for the treatment of head lice in children--melaleuca oil and lavender oil, pyrethrins and piperonyl butoxide, and a "suffocation" product.

BACKGROUND: There are many different types of pediculicides available OTC in Australia. In this study we compare the efficacy and safety of three topical pediculicides: a pediculicide containing melaleuca oil (tea tree oil) and lavender oil (TTO/LO); a head lice "suffocation" product; and a product containing pyrethrins and piperonyl butoxide (P/PB). METHOD: This study was a randomised, assessor-blind, comparative, parallel study of 123 subjects with live head lice. The head lice products were applied according to the manufacturer's instructions (the TTO/LO product and the "suffocation" product were applied three times at weekly intervals according to manufacturers instructions (on Day 0, Day 7 and Day 14) and the P/PB product was applied twice according to manufacturers instructions (on Day 0 and Day 7)). The presence or absence of live lice one day following the last treatment was determined. RESULTS: The percentage of subjects who were louse-free one day after the last treatment with the product containing tea tree oil and lavender oil (41/42; 97.6%) and the head lice "suffocation" product (40/41, 97.6%) was significantly higher compared to the percentage of subjects who were louse-free one day after the last treatment with the product containing pyrethrins and piperonyl butoxide (10/40, 25.0%; adj. p < 0.0001). CONCLUSION: The high efficacy of the TTO/LO product and the head lice "suffocation" product offers an alternative to the pyrethrins-based product. TRIAL REGISTRATION: The study was entered into the Australian/New Zealand Clinical Trial Registry, ACTRN12610000179033.

Validated LC-MS/MS assay for the quantitative determination of vardenafil in human plasma and its application to a pharmacokinetic study.

A sensitive high-performance liquid chromatography-tandem mass spectrometric (HPLC-MS/MS) assay has been developed for the quantitative analysis of vardenafil in human plasma. Vardenafil and the internal standard, alprazolam, were extracted from 0.2 mL aliquots of alkalinized plasma by a single solvent extraction into hexane : dichloromethane. Reversed-phase chromatographic separation was affected by gradient elution with mobile phases consisting of 10 mM ammonium formate pH 7.0 (solvent A) and methanol (100%, solvent B), delivered at a flow rate of 0.4 mL/min. The analytes were detected by using an electrospray ion source on a 4000 QTrap triple quadrupole mass spectrometer operating in positive ionization mode. The mass transitions were m/z 489.3 --> 312.2 for vardenafil and m/z 309.2 --> 281.0 for alprazolam. The assay was linear over the concentration range of 0.2-100 ng/mL, with correlation coefficients > or = 0.995. The intra- and inter-day precision was less than 5.4% in terms of relative standard deviation and the accuracy was within 12.7% in terms of relative error. The lower limit of quantitation was set at 0.2 ng/mL. The high sensitivity and acceptable performance of the assay allowed its application to the analysis of plasma samples obtained following the oral administration of vardenafil to healthy male volunteers in a pharmacokinetic study.

Comparison of a novel HPV test with the Hybrid Capture II (hcII) and a reference PCR method shows high specificity and positive predictive value for 13 high-risk human papillomavirus infections.

BACKGROUND: It is well established that human papillomavirus (HPV) infection is highly related to the development of precursor lesions of cervical cancer and uterine cancers. However, for a pre-cancerous lesion to develop, a persistent infection with a high-risk type HPV is necessary. The Digene Hybrid Capture II (hcII) assay is the only FDA approved method used in conjunction with cytology for HPV screening of women older than 30. The hcII has moderate sensitivity (64.7%) and is dependent on the cellular content of samples, rendering occasionally false positive and false negative results. OBJECTIVE: This study aims to evaluate the performance of a new HPV diagnostic kit (High-Risk HPV detection kit, manufactured by Human Genetic Signatures (HGS), Sydney, Australia). METHODS: The method under evaluation was assessed by comparing the results obtained from testing 834 cervical specimens with the HGS method and the Digene hcII method, using genotyping as the reference standard. RESULTS: Results of the study showed that the specificity and positive predictive value of the HGS High-Risk HPV detection test are significantly greater than those of the Digene hcII test. Overall the HGS HPV assay provides a more accurate system for the detection of high-risk HPV strains, with simpler technical use compared with PCR-sequencing methods.