A Pharmacokinetic Study of Ephedrine and Pseudoephedrine after Oral Administration of Ojeok-San by Validated LC-MS/MS Method in Human Plasma.

A sensitive and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) system was developed and fully validated for the simultaneous determination of ephedrine and pseudoephedrine in human plasma after oral administration of the herbal prescription Ojeok-san (OJS); 2-phenylethylamine was used as the internal standard (IS). Both compounds presented a linear calibration curve (r2 ≥ 0.99) over a concentration range of 0.2-50 ng/mL. The developed method was fully validated in terms of selectivity, lower limit of quantitation, precision, accuracy, recovery, matrix effect, and stability, according to the regulatory guidelines from the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. This validated method was successfully applied for the pharmacokinetic assessment of ephedrine and pseudoephedrine in 20 healthy Korean volunteers administered OJS.

Comparative nasal airflow with loratadine-pseudoephedrine and fluticasone nasal spray for allergic rhinitis.

BACKGROUND: Although it is known that oral antihistamine-pseudoephedrine combination tablets have a faster onset than intranasal corticosteroid sprays in the treatment of allergic rhinitis after the first dose, the magnitude of change has not been measured in a comparative manner. Furthermore, the sensation of sprayed liquid in the nose may lead patients to mistakenly believe that intranasal steroid sprays work instantly. OBJECTIVE: To evaluate, numerically, nasal airflow changes provided by a single dose of loratadine-pseudoephedrine tablet (LP) and fluticasone propionate nasal spray (FP) in participants experiencing allergic rhinitis symptoms, including nasal congestion. METHODS: This single-center, double-blinded, placebo-controlled, crossover study evaluated objective nasal airflow changes in patients with a documented sensitivity to ragweed pollen. Participants were randomized to receive 1 of 4 treatment sequences, and their peak nasal inspiratory flow (PNIF) was measured in a span of 4 hours after pollen exposure in an environmental exposure unit. RESULTS: Average change in PNIF was 31% with LP in the course of the study, significantly greater than with placebo and FP (12% and 15%, respectively; P < .001). Nevertheless, FP did not produce a significant change compared with its placebo. At hour one post-dose, LP had a clinically significant 31% increase in PNIF, whereas FP only yielded an 8.6% increase (P < .001). Measurable nasal airflow improvements are associated with the opening of nasal passages, allowing congested patients to breathe more freely. CONCLUSION: A single dose of LP quickly and significantly (P < .001) improved nasal airflow after ragweed pollen challenge in an environmental exposure unit. Comparatively, FP did not display this same benefit. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03443843.

Bioavailability of Triprolidine as a Single Agent or in Combination With Pseudoephedrine: A Randomized, Open-Label Crossover Study in Healthy Volunteers.

Antihistamines have been in clinical use for more than 70 years to treat allergic and nonallergic symptoms including relief from cold and flu symptoms. Despite their widespread use, pharmacokinetic (PK) data are sparse for older, first-generation antihistamines. This phase 1 single-center open-label, randomized, single-dose, 3-way crossover trial evaluated the PK profiles of 2 doses of film-coated triprolidine caplets (2.5 and 5 mg) compared with a reference combination tablet (triprolidine 2.5 mg + pseudoephedrine 60 mg) in 24 healthy adults. Blood samples were collected predose and at specified intervals across a 24-hour period after administration, and triprolidine was quantified using liquid chromatography-tandem mass spectrometry. Maximum plasma concentration of triprolidine for the 2.5 mg and dose-normalized 5 mg single-agent tablets were comparable (8.4 versus 7.1 ng/mL, respectively) and higher for the combination tablet (9.5 ng/mL). PK parameters, including time to maximum plasma concentration (∼1.5 hours) and elimination half-life (∼4 hours), were comparable between the 3 treatment arms. The safety profile of this sedating antihistamine was as expected; however, adverse effects were reported in a markedly higher proportion of women than men. There were no significant sex differences in any of the measured PK parameters.

Time-to-onset of cold and flu symptom relief: A randomized, double-blind, placebo-controlled pilot study for a multi-symptom combination product.

OBJECTIVE: Evaluate effects of a multisymptom tablet on cold and flu symptoms within 4 hours post-administration. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled study in adults with cold and flu symptoms. Eligible participants with at least moderate common cold or flu symptoms and symptom onset ≤ 48 hours before screening were assigned to a single multiple-active-ingredient tablet (containing paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide, and chlorpheniramine maleate) or placebo tablet. Participants rated severity of each symptom (sore throat, headache, extremity pain, nasal congestion, sneezing, runny nose, and cough) from 0 (absent) to 3 (severe) at 15 and 30 minutes and 1, 2, 3, and 4 hours post administration. The total symptom score (TSS) was calculated as the sum of the individual symptom scores (primary endpoint). Participants rated global response to treatment on a scale from 0 (ineffective) to 4 (excellent). Adverse events (AEs) were recorded throughout. RESULTS: Of 53 participants randomized, 52 received active tablet (n = 25) or placebo tablet (n = 27). Change from baseline in TSS throughout the 4-hour post-administration period was similar between groups. An efficacy criterion of 30% decrease in TSS at assessment points was not met (range, -1.91 to 8.94%). There were also no significant differences between groups in mean symptom scores for individual symptoms or global response to treatment. Four non-serious treatment-emergent adverse events occurred. CONCLUSION: In this exploratory pilot study, a multisymptom cold and flu tablet was well tolerated but did not differ from placebo tablet with regard to onset of action following a single dose.
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Successful Management of Psychotropics Induced Stuttering Priapism with Pseudoephedrine in a Patient with Schizophrenia.

Stuttering Priapism is a recurrent, persistent penile erection in the absence of sexual desire due to altered genital hemodynamics, affecting the arterial component (high flow, non-ischemic) or the veno-occlusive mechanism (low flow, ischemic). Both typical and atypical antipsychotics increase the risk for priapism with greater implications in typicals than atypicals. Prompt recognition and treatment are important as 40% to 50% of patients with stuttering priapism may develop an erectile dysfunction if left untreated. There are several case reports in the literature about the association between psychotropic agents and priapism. However, there are no reports of successfully treating stuttering priapism using pseudoephedrine (sudafed) in the adult population. Here we present successful management of psychotropics induced stuttering priapism with pseudoephedrine in a male patient with schizophrenia.

Efficacy of treatment with pseudoephedrine in men with retrograde ejaculation.

The use of pseudoephedrine, an alpha agonist, for the treatment of retrograde ejaculation is well-known, however, there is no clear consensus from the literature regarding its efficacy and treatment protocol. We evaluated the efficacy of pseudoephedrine treatment in patients with retrograde ejaculation, utilizing a yet undescribed short-period treatment protocol. Twenty men were medically treated with pseudoephedrine for retrograde ejaculation between January 2010 and May 2016 (12 with complete retrograde ejaculation and 8 with partial retrograde ejaculation). All patients had a semen analysis and post-ejaculatory urinalysis before and after treatment. The treatment protocol consisted of 60 mg of pseudoephedrine every 6 h on the day before semen analysis and two more 60 mg doses on the day of the semen analysis. Diabetes was the most common etiology for complete retrograde ejaculation (60%), whereas an idiopathic cause was the most common etiology for partial retrograde ejaculation (82%). Of the 12 complete retrograde ejaculation patients treated with pseudoephedrine prior to semen analysis, 7 (58.3%) recovered spermatozoa in the antegrade ejaculate, with a mean total sperm count of 273.5 ± 172.5 million. Of the eight patients with partial retrograde ejaculation, five (62.5%) had a ≥50% increase in the antegrade total sperm count. In this group, the mean total sperm count increased from 26.9 ± 8.5 million before treatment to 84.2 ± 24.6 million after treatment, whereas the percentage of spermatozoa in the urine declined from 43.2 ± 9% to 17 ± 10%, respectively (both p < 0.05). Overall, in men with retrograde ejaculation treated with a pseudoephedrine regimen prior to ejaculation, some improvement in seminal parameters occurred in 14 (70%) patients, with 10 patients (38.5% of all patients) achieving antegrade total sperm counts over 39 million.

Acute Myocardial Infarction from Coronary Vasospasm Precipitated by Pseudoephedrine and Metoprolol Use.

Pseudoephedrine is a sympathomimetic α- and ß-adrenergic receptor agonist that causes vasoconstriction and reduction in edema throughout the nasal passages. Coronary vasospasm associated with pseudoephedrine has been reported in the literature. We discuss the case of a patient with new-onset atrial fibrillation receiving metoprolol for rate control on a background of pseudoephedrine use for allergic rhinitis leading to acute myocardial infarction from multivessel coronary vasospasm. This case illustrates the importance of understanding the pharmacology of potential drug-drug interactions when managing patients with acute cardiovascular syndromes.

Factors associated with efficacy of an ibuprofen/pseudoephedrine combination drug in pharmacy customers with common cold symptoms.

AIM: The aim of this study was to explore factors affecting efficacy of treatment of common cold symptoms with an over-the-counter ibuprofen/pseudoephedrine combination product. METHODS: Data from an anonymous survey among 1770 pharmacy customers purchasing the combination product for treatment of own common cold symptoms underwent post-hoc descriptive analysis. Scores of symptoms typically responsive to ibuprofen (headache, pharyngeal pain, joint pain and fever), typically responsive to pseudoephedrine (congested nose, congested sinus and runny nose), considered non-specific (sneezing, fatigue, dry cough, cough with expectoration) and comprising all 11 symptoms were analysed. Multiple regression analysis was applied to explore factors associated with greater reduction in symptom intensity or greater probability of experiencing a symptom reduction of at least 50%. RESULTS: After intake of first dose of medication, typically ibuprofen-sensitive, pseudoephedrine-responsive, non-specific and total symptoms were reduced by 60.0%, 46.3%, 45.4% and 52.8%, respectively. A symptom reduction of at least 50% was reported by 73.6%, 55.1%, 50.9% and 61.6% of participants, respectively. A high baseline score was associated with greater reductions in symptom scores but smaller probability of achieving an improvement of at least 50%. Across both multiple regression approaches, two tablets at first dosing were more effective than one and (except for ibuprofen-sensitive symptoms) starting treatment later than day 2 of the cold was generally less effective. DISCUSSION AND CONCLUSIONS: Efficacy of an ibuprofen/pseudoephedrine combination in the treatment of common cold symptoms was dose-dependent and greatest when treatment started within the first 2 days after onset of symptoms.

Nasal decongestants in monotherapy for the common cold.

BACKGROUND: Many treatments for the common cold exist and are sold over-the-counter. Nevertheless, evidence on the effectiveness and safety of nasal decongestants is limited. OBJECTIVES: To assess the efficacy, and short- and long-term safety, of nasal decongestants used in monotherapy to alleviate symptoms of the common cold in adults and children. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 6, June 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Specialised Register, MEDLINE (1946 to July 2016), Embase (2010 to 15 July 2016), CINAHL (1981 to 15 July 2016), LILACS (1982 to July 2016), Web of Science (1955 to July 2016) and clinical trials registers. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs investigating the effectiveness and adverse effects of nasal decongestants compared with placebo for treating the common cold in adults and children. We excluded quasi-RCTs. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted and summarised data on subjective measures of nasal congestion, overall patient well-being score, objective measures of nasal airway resistance, adverse effects and general recovery. One review author acted as arbiter in cases of disagreement. We categorised trials as single and multi-dose and analysed data both separately and together. We also analysed studies using an oral or topical nasal decongestant separately and together. MAIN RESULTS: We included 15 trials with 1838 participants. Fourteen studies included adult participants only (aged 18 years and over). In six studies the intervention was a single dose and in nine studies multiple doses were used. Nine studies used pseudoephedrine and three studies used oxymetazoline. Other decongestants included phenylpropanolamine, norephedrine and xylometazoline. Phenylpropanolamine (or norephedrine) is no longer available on the market therefore we did not include the results of these studies in the meta-analyses. Eleven studies used oral decongestants; four studies used topical decongestants.Participants were included after contracting the common cold. The duration of symptoms differed among studies; in 10 studies participants had symptoms for less than three days, in three studies symptoms were present for less than five days, one study counted the number of colds over one year, and one study experimentally induced the common cold. In the single-dose studies, the effectiveness of a nasal decongestant was measured on the same day, whereas the follow-up in multi-dose studies ranged between one and 10 days.Most studies were conducted in university settings (N = eight), six at a specific university common cold centre. Three studies were conducted at a university in collaboration with a hospital and two in a hospital only setting. In two studies the setting was unclear.There were large differences in the reporting of outcomes and the reporting of methods in most studies was limited. Therefore, we judged most studies to be at low or unclear risk of bias. Pooling was possible for a limited number of studies only; measures of effect are expressed as standardised mean differences (SMDs). A positive SMD represents an improvement in congestion. There is no defined minimal clinically important difference for measures of subjective improvement in nasal congestion, therefore we used the SMDs as a guide to assess whether an effect was small (0.2 to 0.49), moderate (0.5 to 0.79) or large (≥ 0.8).Single-dose decongestant versus placebo: 10 studies compared a single dose of nasal decongestant with placebo and their effectiveness was tested between 15 minutes and 10 hours after dosing. Seven of 10 studies reported subjective symptom scores for nasal congestion; none reported overall patient well-being. However, pooling was not possible due to the large diversity in the measurement and reporting of symptoms of congestion. Two studies recorded adverse events. Both studies used an oral decongestant and each of them showed that there was no statistical difference between the number of adverse events in the treatment group versus the placebo group.Multi-dose decongestant versus placebo: nine studies compared multiple doses of nasal decongestants with placebo, but only five reported on the primary outcome, subjective symptom scores for nasal congestion. Only one study used a topical decongestant; none reported overall patient well-being. Subjective measures of congestion were significantly better for the treatment group compared with placebo approximately three hours after the last dose (SMD 0.49, 95% confidence interval (CI) 0.07 to 0.92; P = 0.02; GRADE: low-quality evidence). However, the SMD of 0.49 only indicates a small clinical effect. Pooling was based on two studies, one oral and one topical, therefore we were unable to assess the effects of oral and topical decongestants separately. Seven studies reported adverse events (six oral and one topical decongestant); meta-analysis showed that there was no statistical difference between the number of adverse events in the treatment group (125 per 1000) compared to the placebo group (126 per 1000). The odds ratio (OR) for adverse events in the treatment group was 0.98 (95% CI 0.68 to 1.40; P = 0.90; GRADE: low-quality evidence). The results remained the same when we only considered studies using an oral decongestant (OR 0.95, 95% CI 0.65 to 1.39; P = 0.80; GRADE: low-quality evidence). AUTHORS' CONCLUSIONS: We were unable to draw conclusions on the effectiveness of single-dose nasal decongestants due to the limited evidence available. For multiple doses of nasal decongestants, the current evidence suggests that these may have a small positive effect on subjective measures of nasal congestion in adults with the common cold. However, the clinical relevance of this small effect is unknown and there is insufficient good-quality evidence to draw any firm conclusions. Due to the small number of studies that used a topical nasal decongestant, we were also unable to draw conclusions on the effectiveness of oral versus topical decongestants. Nasal decongestants do not seem to increase the risk of adverse events in adults in the short term. The effectiveness and safety of nasal decongestants in children and the clinical relevance of their small effect in adults is yet to be determined.

Voiding dysfunction in patients with nasal congestion treated with pseudoephedrine: a prospective study.

BACKGROUND: Pseudoephedrine is a sympathomimetic drug widely used as a nasal decongestant. However, it can cause adverse effects, such as voiding dysfunction. The risk of voiding dysfunction remains uncertain in patients without subjective voiding problems. METHODOLOGY: We prospectively enrolled patients with nasal congestion who required treatment with pseudoephedrine from May to August 2015. All patients denied concomitant subjective voiding problem. The International Prostate Symptom Score (IPSS) questionnaire was used to evaluate voiding function before and 1 week after the pseudoephedrine treatment. The results of the IPSS questionnaire were analyzed as the total (IPSS-T), voiding (IPSS-V), storage (IPSS-S), and quality of life due to urinary symptom scores. RESULTS: We enrolled 131 males with a mean age of 42.0±14.3 years. The IPSS-T, IPSS-V, and IPSS-S scores slightly increased after the medication (IPSS-T increased from 6.49 to 6.77, IPSS-V from 3.33 to 3.53, and IPSS-S from 3.17 to 3.24). The quality of life due to urinary symptom score nonsignificantly decreased from 2.02 to 1.87. We observed that older age and a higher premedication IPSS-V score yielded significant differences (P<0.05) for subclinical voiding dysfunction and unchanged voiding function. In patients aged ≥50 years, the IPSS-T, IPSS-V, and IPSS-S scores significantly increased after the pseudoephedrine treatment (IPSS-T increased from 9.95 to 11.45, IPSS-V from 5.38 to 6.07, and IPSS-S 4.57 to 5.38), whereas the quality of life due to urinary symptom score nonsignificantly decreased from 2.71 to 2.48 (P=0.057). In patients aged <50 years, all scores did not significantly differ. CONCLUSION: Pseudoephedrine treatment for nasal congestion requires extra precautions in males >50 years, even without subjective voiding symptoms.

Correlation between the transdermal characteristics of pseudoephedrine and amygdalin in majiepingchuan in vitro.

OBJECTIVE: To analyze the transdermal profile of pseudoephedrine and amygdalin in the Traditional Chinese Medicine majiepingchuan in rat skin and to reveal their interaction. METHODS: A Franz diffusion cell was used in vitro to evaluate the transdermal parameters of cumulative transdermal flux (Q(tot)), cumulative transmission (T(tot)), and mean penetration rate (Kp) of pseudoephedrine and amygdalin in majiepingchuan. Linear regression analyses of Q(tot) over time of pseudoephedrine vs amygdalin and their ratios was adopted for correlation evaluation. RESULTS: At 1, 2, 4, 6, and 8 h, the Q(tot), T(tot) and Kp of pseudoephedrine showed a good correlation with that of amygdalin. CONCLUSION: There was a small difference in the ratios of Q(tot), T(tot) and Kp between pseudoephedrine and amygdalin, and a correlation between them.

Oral pseudoephedrine decreases the rate of transmucosal nitrous oxide exchange for the middle ear.

OBJECTIVES/HYPOTHESIS: Determine if oral treatment with a vasoconstrictor decreases the blood to middle ear exchange rate of the perfusion-limited gas, nitrous oxide (N2O). STUDY DESIGN: Randomized, double-blind, crossover study. METHODS: Ten adult subjects with and 10 without past middle ear disease completed paired experimental sessions, identical except for oral treatment with either pseudoephedrine hydrochloride or lactose placebo. At each session, subjects were fitted with a nonrebreathing mask and breathed room air for 20 minutes (acclimation period), 50% N2O:50% O2 for 20 minutes (experimental period), and 100% O2 for 10 minutes (recovery period). Throughout, heart rate, blood pressure, and O2 saturation were monitored, and bilateral middle ear pressures were recorded by tympanometry every minute. The primary outcome was the slope of the middle ear pressure-time function for the experimental period, which estimates the volume N2O exchange rate. Using repeated measures analysis of variance, the effects of group (disease history), treatment (active vs. placebo), and period (1 vs. 2) on the recorded vital signs, and of group, treatment, and ear (left/right) on the middle ear pressure-time slope were evaluated for statistical significance. RESULTS: Statistically significant effects of period on O2 saturation (period 2 > period 1) and of treatment on heart rate (active > placebo) were documented. Only treatment was statistically significant for the middle ear pressure-time slope, with a shallower slope characterizing the active treatment session. CONCLUSIONS: The volume exchange rate across the middle ear mucosa of perfusion-limited gases can be modulated pharmacologically. Theoretically, similar drugs can be used to reduce the requisite eustachian tube opening efficiency for adequate middle ear pressure regulation. LEVEL OF EVIDENCE: 1b.

Pseudoephedrine and circadian rhythm interaction on neuromuscular performance.

This study analyzed the effects of pseudoephedrine (PSE) provided at different time of day on neuromuscular performance, side effects, and violation of the current doping cut-off threshold [World Anti-Doping Agency (WADA)]. Nine resistance-trained males carried out bench press and full squat exercises against four incremental loads (25%, 50%, 75%, and 90% one repetition maximum [1RM]), in a randomized, double-blind, cross-over design. Participants ingested either 180 mg of PSE (supra-therapeutic dose) or placebo in the morning (7:00 h; AM(PLAC) and AM(PSE)) and in the afternoon (17:00 h; PM(PLAC) and PM(PSE)). PSE enhanced muscle contraction velocity against 25% and 50% 1RM loads, only when it was ingested in the mornings, and only in the full squat exercise (4.4-8.7%; P < 0.05). PSE ingestion raised urine and plasma PSE concentrations (P < 0.05) regardless of time of day; however, cathine only increased in the urine samples. PSE ingestion resulted in positive tests occurring in 11% of samples, and it rose some adverse side effects such us tachycardia and heart palpitations. Ingestion of a single dose of 180 mg of PSE results in enhanced lower body muscle contraction velocity against low and moderate loads only in the mornings. These mild performance improvements are accompanied by undesirable side effects and an 11% risk of surpassing the doping threshold.

Female clitoral priapism: an over-the-counter option for management.

INTRODUCTION: Female priapism is a rare condition that is not commonly described in the literature. There are many treatment strategies for the management of priapism, including conservative and safe over-the-counter options. AIM: To describe a case of a woman who presented with clitoral priapism, who was managed conservatively with a simple over-the-counter treatment plan. METHODS: A 29-year-old gravida 0 para 0 presented to the emergency room with painful clitoral priapism lasting for 5 days. Despite cessation of the suspected causal agents, trazodone and wellbutrin, her symptoms persisted. RESULTS: The patient was managed conservatively with analgesics and around-the-clock oral pseudoephedrine and experienced complete resolution of her symptoms. CONCLUSIONS: Oral pseudoephedrine may be a reasonable option for certain patients, and may be considered as a first-line therapy and adjunct to conservative measures.

The dose-response relationship between pseudoephedrine ingestion and exercise performance.

OBJECTIVES: The purpose of the present study was to examine a possible dose-response between pre-exercise pseudoephedrine intake and cycling time trial performance. DESIGN: Randomised, double-blind, crossover trial. METHODS: Ten trained male endurance cyclists (26.5 ± 6.2 years, 75.1 ± 5.9 kg, 70.6 ± 6.8 mL kg(-1)min(-1)) undertook three cycling time trials in which a fixed amount of work (7 kJ kg(-1) body mass) was completed in the shortest possible time. Sixty minutes before the start of exercise, subjects orally ingested either 2.3 mg kg(-1) or 2.8 mg kg(-1) body mass of pseudoephedrine or a placebo in a randomised and double-blind manner. Venous blood was sampled at baseline, pre- and post-warm up and post-exercise for the analysis of pH and lactate and glucose concentrations; plasma catecholamine and pseudoephedrine concentrations were measured at all times except post-warm up. RESULTS: Cycling time trial performance (∼ 30 min) was not enhanced by pseudoephedrine ingestion. Plasma pseudoephedrine concentration increased from pre-warm up to post-exercise in both treatment conditions, with the 2.8 mg kg(-1) body mass dose producing the highest concentration at both time points (2.8 mg kg(-1)>2.3 mg kg(-1)>placebo; p<0.001). CONCLUSIONS: There was large individual variation in plasma pseudoephedrine concentration between subjects following pseudoephedrine administration. A number of factors clearly influence the uptake and appearance of pseudoephedrine in the blood and these are not yet fully understood. Combined with subsequent differences in plasma pseudoephedrine between individuals, this may partially explain the present findings and also the inconsistencies in performance following pseudoephedrine administration in previous studies.