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  • 1
    Electronic Resource
    Electronic Resource
    Implantation temperature effect on polycrystalline silicon by ion shower doping (1993)
    [S.l.] : American Institute of Physics (AIP)
    Journal of Applied Physics 74 (1993), S. 7114-7117 
    Details
    ISSN: 1089-7550
    Source: AIP Digital Archive
    Topics: Physics
    Notes: We present a new doping technique using an ion shower doping system with a bucket ion source. Phosphorus atoms were implanted in polycrystalline silicon from room temperature to 300 °C. Sheet resistances were significantly reduced by raising the implantation temperature. With a crystal fraction of 85%, sheet resistance was 5×102 S−1/(D'Alembertian) as implanted. These effects were not due to pure thermal annealing by ion beam heating. A significant improvement was found in sheet resistance as a result of averaging the impurity profile by radiation enhanced diffusion and low temperature recrystallization of the implanted region by collision of atoms.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1063/1.355026
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  • 2
    Electronic Resource
    Electronic Resource
    Human scalp hair as evidence of individual dosage history of haloperidol: a possible linkage of haloperidol excretion into hair with hair pigment (1990)
    Springer
    Archives of dermatological research 282 (1990), S. 120-125 
    Details
    ISSN: 1432-069X
    Keywords: Scalp hair ; Haloperidol ; Segmental analysis ; Dosage history ; Melanin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We report a method for determining haloperidol concentration in human scalp hair and discuss a possible linkage of haloperidol excretion into hair with the hair pigment melanin. First, an animal study was conducted to support the idea that hair contains amounts of haloperidol corresponding to the doses given and pigmented hair contains much more drug than does unpigmented hair. The haloperidol concentration was measured using a radioimmunoassay technique after hairs were dissolved in 2.5 N NaOH solution and the drug extracted. Pigmented and albino rats, whose hair from an area on the back had been removed beforehand by plucking, were administered either 1,3, or 10 mg of haloperidol (i.p.) per kg body weight every day for 3 weeks. At the end of the administration period hair which had newly grown on the denuded area was plucked and collected. In each of the two groups classified by hair color the drug levels in the hair correlated with the doses given; however, the concentrations in the hair from the albino rats were much lower than those in the hair from the pigmented rats (which was less than 8.5%). Second, black and white hair was collected from each of seven human subjects with grizzled hair, who were receiving or had been administered haloperidol at fixed daily doses for more than 1 month, and the concentration of haloperidol in each type of hair was measured. In the same subject the concentration in the white hair was found to be much lower than that in the black (less than 10%). In three subjects the dosage had been changed before the hair samplings, and segmental analysis of the distribution of haloperidol in the black hair revealed that the dosage history was imprinted along the length, assuming a hair growth rate of 1 cm/ month; the distribution of drug along the white hair less obviously corresponded to the dosage. Third, another keratinized tissue, nail, was collected together with hair samples from 20 patients and the haloperidol level in the nail was measured and compared with that in the hair. The concentration of haloperidol in nail is only about 3.4% of that in hair. Taken together these results suggest that the mechanism for excreting haloperidol into hair is closely linked with that for the hair pigment melanin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00493470
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  • 3
    Electronic Resource
    Electronic Resource
    Antiarrhythmic and electrophysiological effects of SD-3212, a novel Na+ and Ca++ channel blocker, in anaesthetized dogs with myocardial infarction in comparison with its stereoisomer (SD-3211) and bepridil (1992)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 345 (1992), S. 688-695 
    Details
    ISSN: 1432-1912
    Keywords: Na+ and Ca++ channel blocker ; Ventricular arrhythmia ; Intraventricular conduction ; Refractory period ; Myocardial infarction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Antiarrhythmic and electrophysiological effects of SD-3212, a novel antiarrhythmic agent, which has both Na+ channel and Ca++ channel blocking activites, were compared with those of its (+)-stereoisomer, SD-3211, which has only a Ca++ channel blocking activity, and bepridil, a known Ca++ channel blocker with additional Na+ channel blocking activity, using the two-stage coronary ligation induced arrhythmia (24h after the ligation of the left anterior descending coronary artery) and 7 day-old myocardial infarcted hearts in anaesthetized dogs. SD-3212 showed a dose-dependent antiarrhythmic effect on the two-stage coronary ligation induced arrhythmia. SD-3212 at a dose of 3 mg/kg reduced the arrhythmic ratio, i.e. ectopic beats per min divided by the sum of ectopic beats and sinus beats per min, significantly from 1 up to 12 min after the administration. Neither bepridil (1–6 mg/kg) nor SD-3211 (1 mg/kg) had an antiarrhythmic effect. SD-3212 (0.3–3 mg/kg) prolonged both the conduction time in the normal myocardium and the delayed potential in the infarcted myocardium in the 7 day-old myocardial infarcted hearts in anaesthetized dogs in a dose-dependent manner. This effect of SD-3212 was shown at coupling intervals of 150–1000 ms increasing with decreasing interval. In this respect, SD-3212 is similar to drugs which show fast recovery of Vmax from use-dependent block such as lidocaine. Bepidril (1–6 mg/kg) also prolonged these parameters in a dose-dependent manner, however, the prolongation induced by bedripil was limited to shorter coupling intervals as compared with that induced by SD-3212. SD-3212 (0.1–1 mg/kg) did not show this prolonging effect. SD-3212 increased the refractory period in the infarcted zone to a small extent (not significantly) at all strengths tested between 0.5–4 mA and also in the normal zone between 0.2–1 mA to an even lesser extent than in the infarcted zone. Bepridil produced a significant increase of refractory period in the infarcted zone. In the normal zone, bepridil produced a non-significant, but greater increase of the refractory period as compared with SD-3212. SD-3211 did not affect the refractory period in the infarcted zone or in the normal zone. None of the three drugs produced a significant change in the excitation threshold. Thus, SD-3212 showed electrophysiological properties of a drug with fast recovery kinetics without producing a significant increase of refractory period, and these properties are very similar to those of class Ib antiarrhythmic agents such as lidocaine. The present study suggests that there might be a possibility of SD-3212 to become a safe and unique antiarrhythmic agent with suppresses both Na+ and Ca++ inward current.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00164584
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  • 4
    Electronic Resource
    Electronic Resource
    Chlorpromazine in human scalp hair as an index of dosage history: comparison with simultaneously measured haloperidol (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 439-444 
    Details
    ISSN: 1432-1041
    Keywords: Chlorpromazine ; Haloperidol ; scalp hair ; melanin ; dosage history
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration of chlorpromazine (CPZ) in hair was measured to demonstrate its value as an index of individual dosage history and compliance. An animal study using pigmented rats was conducted to confirm the dose-dependent accumulation of CPZ in hair. The concentration of CPZ in hair, newly regrown on a denuded area of the back after the administration of CPZ for 3 weeks, was 4.6, 8.5 and 16.6 ng·mg−1 hair after daily doses of 1.25, 2.5 and 5 mg·kg−1·day−1, respectively, significantly correlated with the daily dose. The concentration of CPZ in black hairs collected from 23 Japanese patients, who had been taking CPZ in fixed daily doses (30–300 mg/day), ranged from 1.6 to 27.5 ng·mg−1, and was significantly correlated both with the daily dose and with the trough plasma concentration at steady state. Several strands of hair collected from each of 5 patients, whose doses of CPZ had been changed within several months before sampling, were cut into 1-cm pieces successively from the scalp end and the concentration of CPZ in each piece was measured. With the assumption of a hair growth rate of 1 cm per month, the individual history of CPZ doses in all patients could be deduced from the distribution of CPZ along the hair shaft. In 5 patients with grizzled hair the concentration of CPZ in white hairs was much lower (〈10%) than in black hairs, suggesting that the strong affinity of CPZ for hair melanin may explain the accumulation of CPZ in black hair. The concentration of co-administered haloperidol (HP) in plasma and hair was also measured in 11 out of 23 patients. The CPZ concentration in hair was much lower than that of HP (about 0.3 to 7.8%), whether the comparison was made on the basis of daily dose or plasma concentration. This finding is discussed in relation to the affinity of the compounds for their melanin and photochemical stability.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315540
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  • 5
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of temocapril hydrochloride, a novel angiotensin converting enzyme inhibitor, in renal insufficiency (1992)
    Springer
    European journal of clinical pharmacology 43 (1992), S. 657-659 
    Details
    ISSN: 1432-1041
    Keywords: Temocapril, Renal insufficiency ; angiotensin-I converting enzyme inhibitor, pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I). The pharmacokinetic parameters of the active diacid metabolite, including Cmax, AUC and half-life (t1/2), showed only slight changes between the three groups: AUC (0–∞) was significantly larger in Group III than Group I, and t1/2 tended to be prolonged in Group III, but the change was not significant. The urinary recovery of the diacid was significantly decreased in Group III. (Group I, 28.1 %, Group II, 21.6 %, Group III, 12.8 %). Compared with other ACE inhibitors, which are mainly excreted through the kidney, the plasma concentration of the active diacid metabolite was hardly influenced by renal function. It was speculated that lowering of the dose of temocapril might be recommended only in patients with severe renal insufficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02284968
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  • 6
    Electronic Resource
    Electronic Resource
    The pharmacokinetics of the β2-adrenoceptor agonist, tulobuterol, given transdermally and by inhalation (1993)
    Springer
    European journal of clinical pharmacology 44 (1993), S. 361-364 
    Details
    ISSN: 1432-1041
    Keywords: Tulobuterol ; β2-adrenoceptor agonist ; aerosol inhalation ; transdermal delivery ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the pharmacokinetics of tulobuterol given transdermally or by aerosol inhalation in healthy male volunteers. Tulobuterol was rapidly absorbed after inhalation, with a tmax of 0.8–1.5 h. The Cmax and the AUC increased linearly with dose. Tulobuterol was well absorbed after transdermal administration, with an absorption lag-time of about 4 h. The Cmax and AUC increased linearly with dose and the tmax was about 9–12 h. The mean percentage of drug absorbed during the application of a patch for 24 h was 82–90% after a single dose and 82–85% during repeated dosing. The mean urinary recoveries as unchanged drug after a single inhalation and patch application were 3–4% and 5–6% respectively. Tulobuterol did not accumulate during repeated inhalation or transdermal application. It was well tolerated, except for an increase in heart rate of 10–20 beats · min−1 after five repeated applications of a 4 mg patch.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00316473
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  • 7
    Electronic Resource
    Electronic Resource
    Using ofloxacin as a time marker in hair analysis for monitoring the dosage history of haloperidol (1994)
    Springer
    European journal of clinical pharmacology 47 (1994), S. 195-202 
    Details
    ISSN: 1432-1041
    Keywords: Ofloxacin ; Haloperidol ; Scalp hair ; time marker ; dosage history ; HPLC
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Hair samples were obtained 1–5 months after ingestion of the antimicrobial ofloxacin, which had been given for 1 or 3 days at the commencement of haloperidol administration, or when its dosage was reduced. The axial distribution of ofloxacin, haloperidol and its active metabolite, reduced haloperidol, was analysed in segments from single strands of hair. Ofloxacin was detected where the content of haloperidol and reduced haloperidol along the hair shaft showed a sharp change, corresponding to the change in dose. When we matched the time scale of the dosage history to the growth rate, which was estimated using ofloxacin as the time marker, the distribution of the haloperidol and reduced haloperidol precisely coincided with the rise and fall in the dose of haloperidol. These findings demonstrate that ofloxacin can serve as a time marker when drug distribution along the hair shaft is used to obtain the drug exposure history of an individual.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194972
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  • 8
    Electronic Resource
    Electronic Resource
    Changes in plasma and urinary 11-dehydrothromboxane B2 in healthy subjects produced by oral CS-518, a novel thromboxane synthase inhibitor (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 283-286 
    Details
    ISSN: 1432-1041
    Keywords: Thromboxane synthase inhibitor ; CS-518 ; 11-dehydrothromboxane B2 ; enzyme immunoassay ; thromboxane B2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary When 50 mg CS-518, a novel thromboxane (TX) A2 synthase inhibitor, was orally administered to healthy male volunteers, the plasma concentration of CS-518 peaked after 0.5 h and then decreased with a half-life of 0.44 h. There was no significant change in the plasma concentration of circulating TXB2, whereas that of circulating 11-dehydrothromboxane B2 (11-dhTXB2), an enzymatic metabolite of TXB2, was significantly decreased from 0.5 h to 24 h after administration; the maximal decrease to about 25% of the pre-dose value was found at 6 h. After CS-518 100 mg b.d. for 4.5 days, plasma 11-dhTXB2 was suppressed to the same extent as after the single dose of 50 mg from 6 h after the initial dose throughout the administration period. The urinary excretion of 11-dhTXB2 corrected for the creatinine level was significantly decreased by 70–84% throughout the treatment. These results suggest that CS-518 causes long-lasting inhibition of TXA2 synthase despite its rapid elimination from plasma, and that circulating 11-dhTXB2 in plasma and its urinary excretion can serve as a quantitative index of TXA2 synthase inhibition in vivo by CS-518.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00315398
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  • 9
    Electronic Resource
    Electronic Resource
    Pilot study of the uricosuric effect of DuP-753, a new angiotensin II receptor antagonist, in healthy subjects (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 333-335 
    Details
    ISSN: 1432-1041
    Keywords: DuP-753 ; Uricosuria ; angiotensin II receptor antagonist ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The uricosuric effect of DuP-753, a novel, specific angiotensin II receptor antagonist, has been explored in a healthy male Japanese volunteers, given single oral doses of 25, 50, 100 or 200 mg (n=6), or 100 mg (n=6) or placebo (n=3) once daily for 7 consecutive days. In the single-dose study, serum uric acid measured at 4 h after dosing showed a dose dependent decrease; the reductions from the corresponding pre-dose values were: 0.32 (25 mg), 0.77 (50 mg), 1.25 (100 mg) and 1.33 mg dl−1 (200 mg). The urinary excretion of uric acid within the first 4 h after treatment was also increased in a dose-dependent manner, whereas the urinary excretion of creatinine remained unchanged. In the multiple-dose study, DuP-753 significantly decreased the serum uric acid concentration measured 4 h both after the first (pre-dose value: 5.68 vs 4 h after: 4.48 mg·dl−1) and last administrations (4.42 mg·dl−1). Simultaneously, the ratio of urinary uric acid to creatinine excretion was significantly increased within the first 4 h both after the first (DuP-753: 1.190 vs placebo: 0.576) and last administrations (1.02 vs 0.576). The findings suggest that DuP-753 posesses a uricosuric effect both after single and multiple doses in healthy subjects. The effect should be further examined in hypertensive patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00266358
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  • 10
    Electronic Resource
    Electronic Resource
    The measurement of ofloxacin in hair as an index of exposure (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 581-584 
    Details
    ISSN: 1432-1041
    Keywords: Scalp hair ; ofloxacin ; dosage history ; hair growth rate ; index of exposure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Several strands of hair were collected from each of patients who had been taking ofloxacin against bacterial infections some time in the past. In 10 out of total 14 subjects studied the drug was detected only in the hair portions corresponding to the administration period with the assumption of the hair growth rate of about 1 cm/month. Even in a subject who had received 300 mg/day of ofloxacin only for two days the drug could be detected in the corresponding portion. In 3 subjects the drug was detected in some other portion(s) than the corresponding ones. This might be due to the uncertainty of having used the drug on the other occasion. Only in one subject the dosage history could not be deduced from the drug distribution along hair length. In 3 subjects, who had taken the drug within 1 month, hair samples were collected every month for 3 or 4 consecutive months. The front of drug appearance in hair was clearly shown to move outwards along hair shaft every month at a pace of 1–1.5 cm/month. These results suggest that ofloxacin is excreted into human scalp hair, captured there and moves outwards along the hair shaft at its own growth rate. This leads to the concept that the distribution of ofloxacin along hair length can be used for knowing the individual exposure or non-exposure to the drug, and even for knowing hair growth rate when the innoculation(s) of the drug is strictly supervised and recorded.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00279974
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