Time-dependent kinetics. V: Time course of drug levels during enzyme induction (one-compartment model)

Equations were derived to describe the time course of drug levels during auto- and heteroinduction under a variety of input conditions. These equations were based on a pharmacokinetic theory of induction which assumes that metabolic clearance increases exponentially to a maximum value and that the rate of this increase is governed by the degradation rate constant of the induced enzyme (k). Closed form solutions could be obtained only for intravenous single-dose (case I) and multiple-dose (case IV) administration. For each of the other cases, constant-rate intravenous infusion (case III), oral single-dose administration (case II), and multiple-dose administration (case V), an exact solution (not closed form) and an approximation (closed form) were derived. Two sets of equations were derived for each of the five cases to take into consideration the possibility of a latency term ().Plots of drug amount X(or concentration C) vs. time (t) were constructed. In case I, a log Xvs. tplot was convex, the slope increasing with time. In case II, Xincreased,reached a peak, and decayed as in case I. In case III ( > 5In 2V/Q) Creached a preinduction steady state before decreasing to a lower (induced) steady state. When =0, Creached a maximum before decreasing to the same induced steady state. The behavior of Cvs. tfor cases IV and V was similar to that for case III. Determination of parameters was attempted in case III. Nonlinear least-square fitting of generated data with 3–9% error yielded reasonable estimates of k.This work was supported by NIH Research Contracts N0l-NS-1-2282 and N01-NS-6-2341.Parts I, II, III, IV, and VI of this series can be found in theJournal of Pharmaceutical Sciences.     

Lack of correlation between changes in cyclic nucleotides and subsequent induction of tyrosine hydroxylase in rat adrenal medulla

Summary Pretreatment of rats with dexamethasone (2.5 mol/kg, a dose which blocks the release of ACTH from the pituitary gland) abolished the reserpine-mediated increase in cAMP and the increase in the cAMP/cGMP ratio in the adrenal medulla. In contrast, the reserpine-mediated induction of tyrosine hydroxylase (TH) remained unchanged. Hypophysectomy had a similar effect to dexamethasone treatment. Since changes in cAMP and changes in the cAMP/cGMP ratio are not indispensible prerequisites for the subsequent induction of TH, a causal relationship between the two phenomena seems to be excluded.     

Antitumor Immunity Induction by Intracellular Hyperthermia Using Magnetite Cationic Liposomes

Induction of antitumor immunity to T-9 rat glioma by intracellular hyperthermia using functional magnetic particles was investigated. Magnetite cationic liposomes (MCLs), which have a positive surface charge, were used as heating mediators for intracellular hyperthermia. Solid T-9 glioma tissues were formed subcutaneously on both femurs of female F344 rats, and MCLs were injected via a needle only into the left solid tumors (treatment side). The rats were then divided into two groups, which received no irradiation, or irradiation for 30 min given three times at 24-h intervals with an alternating magnetic field (118 kHz, 384 Oe). On the treatment side, the tumor tissue disappeared completely in many rats exposed to the magnetic field. The tumor tissue on the opposite side also disappeared completely, even though MCLs were not injected into the right solid tumors. To examine whether a long-lasting and tumor-specific immunity could be generated, the rats that had been cured by the hyperthermia treatment were rechallenged with T-9 cells 3 months later. After a period of transient growth, all tumors disappeared. Furthermore, immuno-cytochemical assay revealed that the immune response induced by the hyperthermia treatment was mediated by both CD8⁺ and CD4⁺ T cells and accompanied by a marked augmentation of tumor-selective cytotoxic T lymphocyte activity. These results suggest that our magnetic particles are potentially effective tools for hyperthermic treatment of solid tumors, because in addition to killing of the tumor cells by heat, a host immune response is induced.     

药物代谢中的药酶特性与临床研究近况

目的:为了促进药物代谢酶在临床上的深入研究。方法:以近几年国内外大量有代表性的论文为依据进行分析、归纳、整理。结果:药物代谢酶大多具有遗传多态性,其活性受相关药物影响,遗传多态性和药物之间代谢性相互作用是临床药物反应千变万化的重要因素。结论:药物代谢酶的认识和研究有助于临床合理用药和减少药物不良反应。     

Misoprostol vs. oxytocin for induction of labor at term.

Efficacy of misoprostol was studied for induction of labor at term. Seventy patients were randomized to Group A (n = 36, oral misoprostol 50 microg four hourly to maximum of 5 doses) and B (n = 34, continuous oxytocin infusion). Induction-delivery interval was shorter with misoprostol (7.7 +/- 2.8 h against 14.3 +/- 4.8 h with oxytocin) but the rates of vaginal delivery, cesarean, neonatal outcome variables were similar. Hence, misoprostol is an effective agent for induction of labor at term.     

Laparoscopic ovarian drilling for women with anovulatory polycystic ovarian syndrome: a district general hospital experience

This is a retrospective study involving 100 anovulatory women with polycystic ovarian syndrome (PCOS) who had laparoscopic ovarian drilling (LOD) between January 1995 and May 2002 at the Royal Berkshire Hospital, Reading, a large district general hospital (DGH). The aim was to evaluate the efficacy of LOD in the treatment of women with anovulatory PCOS in a DGH setting. We also looked at the factors predicting the clinical outcome to be able to counsel the patients pre-operatively. The study showed that the spontaneous pregnancy rate after LOD was 32.46%. A further 28.5% conceived after induction of ovulation with clomiphene citrate (CC) or purified follicular stimulating hormone (Metrodin HP), with a cumulative pregnancy rate of 74%. We did not find a significant difference in the luteinising hormone to follicular stimulating hormone (LH:FSH) ratio of greater than 2.5, LH level of greater than 10 IU/l, body mass index (BMI), age or duration of infertility between the group of women who conceived and those who failed to conceive, in response to LOD.     

Safety of vaginal birth after cesarean delivery.

OBJECTIVE: To compare the outcomes of labor induction in women with a history of 1 cesarean section (CS) who undergo trial of labor. METHODS: A prospective observational study of 702 pregnant women who had 1 previous CS was conducted at Women's Hospital, Hamad Medical Corporation, Doha, Qatar, between April 2003 and April 2004. Those with no history of vaginal delivery were assigned to one group and those with a history of vaginal delivery were assigned to another group, and the latter group was then divided into 2 subgroups according to the results of trial of labor. RESULTS: Of these 702 women with a history of 1 CS, 62.4% also had a history of vaginal delivery. After trial of labor, vaginal delivery occurred more often among women with no history of vaginal delivery (64.8%). Moreover, trial of labor resulted in a vaginal delivery more often in women who were delivered only once and by CS (87.7%) than in women who also had a history of vaginal delivery (79.2%). CONCLUSION: These findings indicate that women who have had a CS should strongly consider natural delivery for subsequent pregnancies.     

舌下含服米索前列醇配伍米非司酮在终止早孕中的应用

目的 :探讨舌下含服米索前列醇配伍米非司酮用于早孕流产的可行性、安全性及有效性。方法 :将孕周在 7wk内的孕妇随机分为舌下组、口服组各 12 0例。 2组均经米非司酮预治疗后 ,舌下组含服米索前列醇 2 0 0 μg ,1h后重复 ,总量不超过6 0 0 μg ;口服组单次口服米索前列醇 6 0 0 μg。 结果 :舌下组完全流产率比口服组高 ,清宫率比口服组低 (P均 <0 0 1) ,引 -流时间缩短 (P <0 0 1) ,阴道流血及药物不良反应两者无明显差异。结论 :舌下组终止早孕具有简便、有效 ,引 -流时间短等优点     

双球囊导管用于瘢痕子宫足月引产的临床观察

目的 探讨瘢痕子宫使用双球囊导管促宫颈成熟及引产后阴道分娩的安全性和有效性.方法 以2016年1月—2018年7月本院收治有阴道分娩条件和意愿的59例宫颈未成熟的足月瘢痕子宫作为研究组,以同期分娩的67例足月非瘢痕子宫宫颈未成熟的为对照组,两组均使用双球囊导管促宫颈成熟及引产,比较两组的母婴结局.结果 研究组孕产妇的年...