Pregnancy in tacrolimus-treated transplant recipients resulted in a favourable outcome. Complications of the mother and neonate were similar to those previously described with other immunosuppressants.

The main purpose of this study was to investigate judgments made by employees from the pharmaceutical industry and allied health‐care sectors in a set of four different drug discovery and development cases derived from real scenarios. Each case study related to go/no‐go decisions taken from various steps in drug discovery through preclinical and clinical development (investigational new drug) on to market introduction (new drug application) and treatment of the target population. Using a web‐based questionnaire, 52 respondents made five sets of judgment within each drug case whether to continue or halt further project development. For each case, additional details of the developmental scenario were disclosed to the respondent after completion of each judgment response. We also assessed to what extent the individual judgments given by the respondents were influenced by work experience and functional role, education, or their perceived entrepreneurial character. Our study demonstrates that health‐care employees differ substantially in their individual intuitive judgments of benefit and risk in go/no‐go decisions during the drug discovery and development process. This lack of coherence and wide variability with respect to the drug development cases selected may reflect judgment in the real world. Such judgments are usually taken from incomplete information, and individual decision‐making rules vary substantially between experts in the field. Further knowledge about this inherent human functional judgment variability may be helpful to form a better understanding of individual decision‐making in relation to inherent uncertainties. Additional research may also clarify how personal experience within drug discovery and development influences judgment and help to optimize decision outcomes in the drug development sector. Importantly, a deeper insight of the fundamentals and rules that shape individual and group decision‐making of everyday drug discovery and development may help to optimize the decision processes in the pharmaceutical industry.

The aim of this paper is to provide a summary of clinical findings regarding the safety of tacrolimus in pregnancy. From 1992 to 1998 data were collected on 100 pregnancies from 84 mothers who received tacrolimus systemically; 83 cases of solid organ transplantation, and 1 case of Behçet's disease. Maternal mean age at conception was 28 years and pregnancy outcome was live birth in 68%, spontaneous abortion in 12%, induced abortion in 12%, stillbirth/perinatal death in 3%, ongoing pregnancy in 2%, and lost to follow up in 3%. Fifty-nine percent of the neonates were delivered prematurely (< 37 weeks of gestation). Birth weight was appropriate for the gestational age in 90% of the cases. Malformations occurred in 4 neonates: case 1, meningocele and urogenital defects; case 2, alcoholic embryopathy; case 3, ear defect, cleft palate and hypospadia; case 4, multicystic dysplastic kidney. There was no consistent pattern of malformations and 2 mothers subsequently delivered a healthy neonate while on tacrolimus therapy. Nearly 70% of pregnancies following systemic tacrolimus administration resulted in a favourable outcome without any significant effect on intrauterine growth. The incidence of malformations was similar to that reported with other immunosuppressants in transplant recipients.

The aim of this paper is to provide a summary of clinical findings regarding the safety of tacrolimus in pregnancy. From 1992 to 1998 data were collected on 100 pregnancies from 84 mothers who received tacrolimus systemically; 83 cases of solid organ transplantation, and 1 case of Behçet's disease. Maternal mean age at conception was 28 years and pregnancy outcome was live birth in 68%, spontaneous abortion in 12%, induced abortion in 12%, stillbirth/perinatal death in 3%, ongoing pregnancy in 2%, and lost to follow up in 3%. Fifty-nine percent of the neonates were delivered prematurely (< 37 weeks of gestation). Birth weight was appropriate for the gestational age in 90% of the cases. Malformations occurred in 4 neonates: case 1, meningocele and urogenital defects; case 2, alcoholic embryopathy; case 3, ear defect, cleft palate and hypospadia; case 4, multicystic dysplastic kidney. There was no consistent pattern of malformations and 2 mothers subsequently delivered a healthy neonate while on tacrolimus therapy. Nearly 70% of pregnancies following systemic tacrolimus administration resulted in a favourable outcome without any significant effect on intrauterine growth. The incidence of malformations was similar to that reported with other immunosuppressants in transplant recipients.

1Ro 31-6930 (0.001-0.3 MM), cromakalim (0.03-3.0OUM), salbutamol (0.001-0.3 pM) and theophylline (0.3-100pM) evoked dose-related reductions in guinea-pig spontaneous tracheal tone with IC,0 values of 0.044, 0.20, 0.021 and 21.OpM respectively. All four agents also relaxed tone supported by betahistine, carbachol, 5-hydroxytryptamine (5-HT), leukotriene D4 (LTD4), U46619 and prostaglandin D2 (PGD2). The order of potency of tracheal relaxants was always salbutamol > Ro 31-6930 > cromakalim > theophylline. 2 All four agents evoked dose-related reductions in 5-HT-and histamine-induced bronchoconstriction in pithed vagotomised guinea-pigs. The dose of Ro 31-6930 producing 50% inhibition of a 5-HT bronchoconstriction was 11.6 pgkg-' and the dose producing 50% inhibition of a histamine bronchoconstriction was 4.4pgkg-. Salbutamol was approximately 4-5 times more potent than Ro 31-6930 whilst cromakalim was approximately 10 times less potent than Ro 31-6930 as a bronchodilator. Theophylline was markedly less potent than any of the other agents. 3 Ro 31-6930, cromakalim, salbutamol and theophylline each protected conscious guinea-pigs from histamine-induced respiratory distress. Ro 31-6930 and salbutamol were each effective at oral doses of 1.0 and 3.Omgkg-1 whilst cromakalim was effective at oral doses of 3.0 and 10.0mgkg-'. Theophylline showed activity only at 300 mg kg-1 p.o. 4 Ro 31-6930 is a novel potassium channel opener which is a potent relaxant of guinea-pig tracheal smooth muscle in vitro and a bronchodilator in vivo.