Despite selling at substantial discounts, private placements of equity are associated with positive abnormal returns. We find evidence that discounts reflect information costs borne by private investors and abnormal returns reflect favorable information about firm value. Results are consistent with the role of private placements as a solution to the Myers and Majluf underinvestment problem and with the use of private placements to signal undervaluation. We also find some evidence of anticipated monitoring benefits from private sales of equity. For the smaller firms that comprise our sample, information eflects appear to be relatively more important than ownership effects.EQUITY PRIVATE PLACEMENT IS among the least-studied methods of corporate capital raising. The few studies that have been published raise provocative questions. An early study by the SEC (1971) reports average discounts of about 30 percent for private placements of unregistered shares. A few small scale studies in the tax-accounting literature find discounts on unregistered shares can exceed 50 percent (Arneson (1981a, 1981b), Friedlob (1983), and Johnson and Racette (1981). In more recent studies, Wruck (1989) reports smaller but still substantial average discounts and Silber (1991) reports discounts on restricted stock averaging 34 percent. Although the illiquidity associated with unregistered stock provides a partial explanation, it is not clear why investors require, and firms are willing to accept, such sizeable discounts. Nor is it clear why registered shares often are privately placed at substantial discounts. The stock price reaction to private placement announcements is also puzzling. Wruck, for example, finds positive announcement period abnormal returns averaging 4.4 percent.^ The positive reaction contrasts with the negative market reaction to public equity issue announce-

ABSTRACT:Prasugrel, a prodrug, is a novel and potent inhibitor of platelet aggregation in vivo. The metabolism of prasugrel and the elimination and pharmacokinetics of its active metabolite, 2-[1-[2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4-mercapto-3-piperidinylidene]acetic acid (R-138727), three inactive metabolites, and radioactivity were determined in five healthy male subjects after a single 15-mg (100 Ci) Clopidogrel and ticlopidine are thienopyridine prodrugs that are activated in vivo to pharmacologically active metabolites that bind irreversibly to the platelets' P2Y 12 receptor, thus inhibiting platelet aggregation. Studies with [14 C]clopidogrel showed that the major metabolic pathway in humans is hydrolysis of clopidogrel to an inactive acid analog; no further metabolites were reported (Lins et al., 1999). Prasugrel (Fig. 1) is a novel and potent thienopyridine prodrug that also inhibits platelet aggregation in vivo. The structure of the thiol-containing active metabolite of prasugrel, R-138727, was previously reported (Sugidachi et al., 2000(Sugidachi et al., , 2001. Similarly, the structure of the thiol-containing active metabolite of clopidogrel was determined by in vitro studies (Pereillo et al., 2002). The platelet-inhibitory activity of prasugrel and initial pharmacokinetic data were recently reported . In vivo, prasugrel is rapidly hydrolyzed to a pharmacologically inactive thiolactone (R-95913), followed by cytochrome P450-dependent ring opening to form the active metabolite R-138727 (Rehmel et al., 2006). The active metabolite of prasugrel possesses two chiral centers, and its four isomers were shown to possess varying degrees of activity toward inhibition of platelet aggregation (Hasegawa et al., 2005).The prasugrel metabolites measured in human plasma in initial studies (Asai et al., 2006) indicated that after formation of R-95913, two thiol-containing compounds are formed, R-138727 and M4, which are further metabolized by S-methylation to R-106583 and R-100932, or conjugation with cysteine to R-119251 and R-118443 (Fig. 1). Compounds R-95913, R-106583, and R-100932 were measured in plasma as indicators for absorption and exposure to prasugrel and its active metabolite. In this report, the physiologic disposition of prasugrel in healthy subjects following a 15-mg (100 Ci) p.o. dose of [14 C]prasugrel is presented. Materials and MethodsRadiolabeled Drug and Chemicals. Prasugrel hydrochloride was provided by Sankyo Co., Ltd. (Tokyo, Japan). Article, publication date, and citation information can be found at

The measured context-sensitive half-times were in close agreement with the context-sensitive half-times previously modelled for these drugs. The results of this study confirm the value of the context-sensitive half-time in describing drug offset compared to the terminal elimination half-life.

Orbofiban is both an antagonist and a partial agonist of platelet GPIIb/IIIa. At low concentrations of the drug, this partial agonist activity may enhance platelet aggregation. Along with suboptimal plasma drug levels, these findings may help explain the lack of efficacy seen with orbofiban in patients with ACS.

The metabolism and elimination of 14C-labelled trimethylamine and its N-oxide (100 mg orally) were studied in three male volunteers. For both compounds the urine was the major route of elimination, with 95% of the administered 14C being voided in the first 24 h. No radioactivity was found in expired air. The majority (greater than 95%) of the urinary 14C from both compounds was excreted as trimethylamine N-oxide.

SUMMARY Debrisoquine and sparteine tests were carried out in 215 random white British subjects. There is a high degree of correlation between the urinary 'metabolic ratios' of the two drugs. New A polymorphism has also been described for the metabolism of sparteine, an alkaloid which has been used as an anti-arrhythmic and oxytocic drug. One phenotype with a frequency of 0-05 in the German population was unable to metabolise the compound. The other phenotype produced two substances thought to result from N-oxidation. The limited amount of pedigree information previously available suggested that 'non-metabolisers' might be autosomal recessives, homozygous for an allele with a frequency of 0-22.23 This paper presents information to show (1) the manner of inheritance of sparteine metabolism, (2) the relationship between the genetic control of 4-hydroxylation of debrisoquine and the metabolism of sparteine, and (3) the use of improved methods for the analysis of bimodal (and trimodal) frequency distributions. MethodsThe debrisoquine phenotyping test' and the analytical procedure5 were carried out as previously described.Received for publication 10 September 1982. Accepted for publication 19 February 1983. The sparteine phenotyping test2 was carried out as follows. Subjects who had fasted overnight ingested a 100 mg capsule of sparteine sulphate. They remained in the fasting state for a further 2 hours thereafter and were then allowed normal food and drink. The urine excreted 11 to 13 hours after drug ingestion was collected for analysis. The analytical procedure3 was carried out as described previously. The areas of the gas liquid chromatography peaks for sparteine, 2-dehydrosparteine, and 5-dehydrosparteine were measured. The 'metabolic ratio' was calculated as: area of sparteine peak sum of areas of peaks of 2-dehydrosparteine and 5-dehydrosparteine. POPULATION SURVEY OF UNRELATED WHITE BRITISH SUBJECTSA total of 215 healthy unrelated adult subjects (who had given informed consent) were tested with both compounds, with intervals of at least 4 days being allowed between the two tests.The families studied whose members were tested with the two drugs were obtained by two methods of ascertainment. (1) Some of the families published in a previous report1 were studied because they contained a debrisoquine 'poor metaboliser', found in the population survey of unrelated white British adult subjects. (2) Other families were investigated because they contained a proband who was found in the present population sample of unrelated British 321 on 11 May 2018 by guest. Protected by copyright.

Cameron lesions are linear gastric ulcers or erosions on the mucosal folds at the diaphragmatic impression in patients with a large hiatal hernia. The clinical relevance of Cameron lesions is due to their potential complications such as gastrointestinal bleeding (acute, chronic and obscure) and anemia. The diagnosis is usually made during upper endoscopy. Medical therapy is the mainstay of treatment with few cases reserved for surgical correction.

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