OBJECTIVETo study the effect of phenformin hydrochloride that may be illegally added in traditional Chinese medicine preparations on the pharmacokinetics of puerarin in rats.

METHODRats were randomly divided into the single pueraria group and the phenformin hydrochloride combined with pueraria group. After oral administration in the two groups, their bloods were sampled at different time points to determine the drug concentration of puerarin in rat blood and calculate pharmacokinetic parameters.

RESULTAfter oral administration with pueraria extracts and phenformin hydrochloride combined with pueraria extracts, the two groups showed main pharmacokinetic parameters as follows: Cmax were (2.39 +/- 1.01), (1.03 +/- 0.35) mg x L(-1), respectively; Tmax were (0.50 +/- 0.09), (1.5 +/- 0.5) h, respectively; Ke were (0.153 +/- 0.028), (0.172 +/- 0.042) h(-1), respectively; t(1/2) were (4.65 +/- 0.86), (4.20 +/- 0.81) h, respectively; AUC(0-t), were (5.73 +/- 2.60), (5.45 +/- 1.81) mg x h x L(-1), respectively; AUC(0-infinity) were (6.72 +/- 2.89), (6.26 +/- 1.88) mg x h x L(-1), respectively. Compared with the single puerarin group, the Cmax was significantly decreased (P < 0.05) and the Tmax was markedly longer (P < 0.01) than the hydrochloride combined with pueraria group.

CONCLUSIONPhenformin hydrochloride can slow down the absorption process of puerarin and change the pharmacokinetic process of puerarin to some extent.

Administration, Oral ; Animals ; Drug Interactions ; Hypoglycemic Agents ; administration & dosage ; pharmacology ; Isoflavones ; administration & dosage ; pharmacokinetics ; Male ; Phenformin ; administration & dosage ; pharmacology ; Rats ; Rats, Wistar ; Vasodilator Agents ; administration & dosage ; pharmacokinetics

AIMTo investigate the effect of nimodipine (NM) on cerebral blood flow (CBF) in dogs following intranasal administration.

METHODSNM solution was administered intranasally, intravenously (i.v.), and orally to dogs and the change of CBF was determined by using electromagnetic blood flowmeter. MFLab experimental program was applied to monitor the experimental process and analyze data.

RESULTSCBF markedly increased after iv and intranasal application, while large variance was observed after oral dosing. CBF in dogs after three administrations increased by 26.4%, 28.0% and 8.5%, respectively, compared with that of baseline. Following intranasal administration, the onset of action was slightly slower than that after iv injection [(5 +/- 4) min vs (2.2 +/- 1.2) min], however the duration of improvement was the longest [ (25 +/- 17) min].

CONCLUSIONIntranasal delivery for NM can be a promising alternative to parenteral or oral administration.

Administration, Intranasal ; Administration, Oral ; Animals ; Blood Flow Velocity ; drug effects ; Cerebrovascular Circulation ; drug effects ; Dogs ; Female ; Injections, Intravenous ; Male ; Nimodipine ; administration & dosage ; pharmacology ; Vasodilator Agents ; administration & dosage ; pharmacology

AIMTo determine the effect of sildenafil citrate on the nocturnal penile erections (i.e. time to onset, the duration of erection, and the interval between first and second erections) of healthy young men.

METHODSTwenty-two potent men, 23-29 years old, were recruited for the study. All subjects completed three sessions over consecutive nights using the RigiScan monitoring device (Dacomed, Minneapolis, USA). After a first night of adaptation, night 2 records were their baseline values, and on night 3 they received 100 mg of sildenafil citrate. Statistical comparisons were done between the second and third night data.

RESULTSThe mean time to onset of the first erection with sildenafil citrate was (34+/-18) min, whereas it was (74+/-24) min (P 0.0001) without sildenafil citrate. The number of erections observed during the first 5 h after sildenafil citrate medication was 3.6+/-0.5 in contrast to 2.4+/-0.5 with no medication (P=0.001). The interval between first and second erections was shorter with sildenafil citrate: (52+/-26) min vs. (85+/-34) min (P = 0.01). The duration of the last erection was statistically significantly longer with the sildenafil citrate: (64 +/-33) min vs. (42 +/-28) min (P 0.001).

CONCLUSIONHealthy young men achieved erection within 34 min after sildenafil citrate administration, which is shorter than the 1 h interval proposed by the manufacturer. The interval between the first and second erections was shorter and the duration of the last nocturnal erection was longer.

Administration, Oral ; Adult ; Humans ; Male ; Penile Erection ; drug effects ; Piperazines ; administration & dosage ; Purines ; Sildenafil Citrate ; Sulfones ; Time Factors ; Vasodilator Agents ; administration & dosage

OBJECTIVESTo evaluate the efficacy of intrameatal application of low dosage alprostadil (PGE1) cream (300 mcg) for the treatment of erectile dysfunction (ED).

METHODSA total of 43 ED patients were selected in the study based on the inclusion criteria. All of the patients signed informed consent forms and entered a 4-week open-label clinical study. A dosage of 300 mg PGE1 in 75 mg cream was applied intrameatally.

RESULTSThe results showed that the primary efficacy (IIEF Q3 + Q4) reached 70.73% after application of the cream. The successful intercourse rate was 86.41%. Based on the GAQ (global assessment Question); 73.17% of the patients were satisfied with their sexual life. At the same time, all of the secondary criteria supported the primary efficacy results. Two patients withdrew during the study period. Six patients (14.63%) had urethral pain or penile redness, which were mostly mild and transient.

CONCLUSIONSWith intrameatal low dosage (300 mcg PGE1) of the PGE1 cream can achieve an equivalent efficacy as that with the full dosage.

Adult ; Aged ; Alprostadil ; administration & dosage ; therapeutic use ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Middle Aged ; Penile Erection ; drug effects ; Treatment Outcome ; Vasodilator Agents ; administration & dosage ; therapeutic use

OBJECTIVETo explore the effects of low-dose oral tadalafil on self-esteem, confidence and sexual relationship in ED patients.

METHODSWe treated 17 ED patients with oral tadalafil at the low dose of 5 mg once daily for 12 weeks, and used the paired t test to compare their scores on The Self-Esteem and Relationship Questionnaire (SEAR) and IIEF-5 and the results of nocturnal penile tumescence (NPT) obtained by nocturnal electrobioimpedance volumetric assessment (NEVA) before and after the medication.

RESULTSThe scores on SEAR and IIEF-5 were significantly increased (P < 0.01) and NPT markedly improved (P < 0.05) after tadalafil treatment as compared with the baseline.

CONCLUSIONLow-dose oral tadalafil once daily can significantly improve the self-esteem, confidence, sexual relationship satisfaction and NPT of ED patients.

Adult ; Carbolines ; administration & dosage ; therapeutic use ; Erectile Dysfunction ; drug therapy ; psychology ; Humans ; Male ; Middle Aged ; Self Concept ; Surveys and Questionnaires ; Tadalafil ; Vasodilator Agents ; administration & dosage ; therapeutic use

OBJECTIVETo investigate the effect of verapamil on the pharmacokinetics of puerarin in rats.

METHODPuerarin with or without verapamil was administered intravenously or orally to rats. The concentration of puerarin in serum was determined by HPLC.

RESULTNo significant difference was found between the control and 0.5 microg x g(-1) verapamil combined groups for intravenous administration, and there was significant difference between the control and 2. 5 microg x g(-1) verapamil combined groups (P < 0.05). When puerarin was administered orally with verapamil, significant difference was found between the control and combined groups (P < 0.05).

CONCLUSIONVerapamil inhibited puerarin metabolism when puerarin was coadministered with verapamil, so it is necessary to change the therapeutic dose of puerarin.

Administration, Oral ; Animals ; Chromatography, High Pressure Liquid ; Drug Interactions ; Isoflavones ; administration & dosage ; blood ; pharmacokinetics ; Male ; Rats ; Vasodilator Agents ; pharmacokinetics ; pharmacology ; Verapamil ; pharmacology

OBJECTIVESyncope is one of the common problems in clinical pediatrics. In recent years, vasovagal reflex was identified as the most common reason for unexplained syncope. Head-up tilt test (HUT) was regarded as one of the important diagnostic criteria. But the sensitivity of baseline head-up tilt test (BHUT) is low. To improve the sensitivity of HUT, we evaluated the diagnostic value of head-up tilt testing potentiated with sublingual nitroglycerin (SNHUT) in children with unexplained syncope.

METHODSTwenty-five patients (11 male and 14 female, mean age 11.8 +/- 2.1 years, ranged from 8 to 15) with unexplained syncope and 10 healthy children in control group (5 male and 5 female, mean age 11.4 +/- 2.1 years, ranged from 9 to 15) were studied. The patients and healthy children were tilted upright to 60 degrees for 45 minutes at BHUT. If syncope did not occur, sublingual nitroglycerin (4 - 6 microg/kg, maximum dose 300 microg) was administered, and continued at same degree for 20 minutes.

RESULTSCompared with controls, there was no significant difference in sex, age, supine blood pressure and supine heart rate of syncopal group (P > 0.05). During BHUT, 12 patients (48%) and none of the controls had positive response, whereas another 8 patients and 2 controls had positive response during SNHUT. In syncopal group, total positive rate was 80%. The sensitivity, specificity, and diagnostic value of SNHUT were all 80%. During SNHUT, the mean time to positive response was 5.9 +/- 2.9 minutes (from 4 to 11 minutes), and only 1 patient had mild headache.

CONCLUSIONHead - up tilt testing potentiated with sublingual nitroglycerin (4 - 6 microg/kg, maximum dose 300 microg) as pharmacological provocation test was a useful and an objective diagnostic tool for evaluating vasovagal syncope in children.

Adolescent ; Child ; Diagnostic Techniques and Procedures ; Female ; Humans ; Male ; Nitroglycerin ; administration & dosage ; Posture ; Sensitivity and Specificity ; Syncope, Vasovagal ; diagnosis ; Vasodilator Agents ; administration & dosage

OBJECTIVETo evaluate the effect of external use of papaverine cream on enhancement of tissue expansion.

METHODS8 mini pigs were randomly divided into 4 groups. During inflation, papaverine was given externally in group A, through a delivery system in group B, though intramuscular injection in group C. Papaverine was not given in group D. The time of inflation, the expansion rate, the surviving length of expanded flaps and the papaverine concentration in the fibrous capsule in each group were examined. Histologic and electroscope examinations of the expanded tissue were made.

RESULTSThe average inflation time was 28.9 +/- 4.5 days in group A, 34.0 +/- 2.6 days in group B, 37.6 +/- 4.8 days in group C and 38.5 +/- 3.5 days in group D. There was significant difference between each group(P < 0.05). The average surviving length of expanded flaps in group A was 13.67 +/- 1.28 cm, 11.07 +/- 0.88 cm in group B, 10.79 +/- 0.49 cm in group C, and 9.49 +/- 0.77 cm in group D. There was significant difference between each group (P < 0.01). Histologic examinations of the expanded tissue suggested that there were no significant differences in thickness of epidermis, derma and fibrous capsule among the four groups. Electroscope examinations of the myofibroblast in fibrous capsule showed that there were smaller nuclei, fewer microfilaments and fewer mitochondrias and rougher endoplastic reticulume in group A than those in other groups. The concentration of papaverine in fibrous capsule of group A was 3.5 +/- 1.2 micrograms/g. Papaverine was detected neither in the skin of other groups nor in the blood of all groups.

CONCLUSIONS1. Papaverine cream can permeate through skin and maintain high concentration and continuous effect in local tissue. 2. External use of papaverine cream can inhabit the function of myofibroblast in fibrous capsule, increase inflation rate, accelerate expansion process, and improve microcirculation of the expanded skin with a result of prolongation of surviving length of expanded flaps. 3. The technique of enhancing tissue expansion with external use of papaverine has the advantages of convenient delivery, cheapness, no more injury and infection, and no side effects etc. It is a safe, effective, simple, and reliable method for accelerating tissue expansion.

Animals ; Papaverine ; administration & dosage ; pharmacokinetics ; Skin ; drug effects ; Surgical Flaps ; Swine ; Swine, Miniature ; Time Factors ; Tissue Expansion ; Vasodilator Agents ; administration & dosage

Objective: To evaluate the effects of three different medications with tadalafil on erectile dysfunction (ED) in young men with primary sexual failure. METHODS: This study included 76 male ED patients aged 21－35 years who had primary sexual failure but normal nocturnal penile tumescence and rigidity and failed to respond to psychotherapy. We randomly assigned them to receive oral tadalafil once daily, on demand, or once-daily + on-demand. After 2－3 months of treatment, we evaluated the effects based on the scores of the patients in the five domains of the International Index of Erectile Function (IIEF-5). RESULTS: After medication, all the patients showed significantly increased scores in the four domains of IIEF-5, namely, erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction. The on-demand group achieved even higher scores in erectile and orgasmic functions but a lower score in sexual desire than the once-daily group. However, the patients in the once-daily + on-demand group exhibited more significant improvement than those in the other two in all the five domains. CONCLUSIONS Once-daily + on-demand medication with tadalafil can significantly enhance the therapeutic effect on psychogenic ED in young men with primary sexual failure.
Adult ; Coitus ; Double-Blind Method ; Drug Administration Schedule ; Erectile Dysfunction ; drug therapy ; psychology ; Humans ; Male ; Orgasm ; Patient Satisfaction ; Penile Erection ; physiology ; Tadalafil ; administration & dosage ; Treatment Outcome ; Urological Agents ; administration & dosage ; Vasodilator Agents ; administration & dosage ; Young Adult

OBJECTIVE: To evaluate the applicability of carotid Doppler echography for the assessment of changes of peripheral hemodynamics in the hypertensives. SUBJECTS: 28 hypertensives (17 males, 11 females), mean age of 64 yrs and 40 normal controls (24 males, 16 females) mean age of 49 yrs. METHODS: We recorded the right common carotid arterial Doppler flow velocity (BFV) pattern and measured the peak velocities of the percussion wave (P) and late rising tidal wave (T), the ratio of the two (P/T), the time interval between the two peaks corrected by heart rate (P-Tc), systolic flow velocity integral (FVI) and carotid artery diameter (CAD) before and after 0.4 mg dose of subligual nitroglycerin (NTG). RESULTS: 1) In hypertensives, the P wave velocity showed lower and P-Tc interval shorter than those of the normal controls at baseline. 2) After NTG, the P-Tc and P/T increased, but the T and FVI decreased significantly in both groups of subjects. 3) The P/T ratio was less significantly increased after NTG in the hypertensives than in the controls. These results suggest that NTG might have been involved in concomitant reduction and delay of the wave reflection from the peripheral vessels, preferentially in the normal subjects than in hypertensives. CONCLUSIONS: The carotid Doppler echography can be useful for the evaluation of the changes of hemodynamics in the peripheral vessel such as carotid artery in hypertensive subjects.
Administration, Sublingual ; Blood Flow Velocity/drug effects ; Carotid Arteries/ultrasonography ; Carotid Arteries/drug effects ; Case-Control Studies ; Female ; Human ; Hypertension/ultrasonography ; Hypertension/physiopathology* ; Hypertension/drug therapy* ; Male ; Middle Age ; Nitroglycerin/administration & dosage* ; Ultrasonography, Doppler, Color ; Vasodilator Agents/administration & dosage*