Interaction between valproic acid and acyclovir after intravenous and oral administration in a rabbit model

This study was undertaken to investigate the effect of co-administration of valproic acid and acyclovir on the pharmacokinetic parameters of each other. Fifteen white New Zealand rabbits were divided into three groups: A, B and C. Group A received acyclovir only, group B received valproic acid only and group C received a combination of acyclovir and valproic acid. In a cross-over design, the intravenous route was studied first, followed by the oral route after a 2-week wash-out period. Blood samples were drawn over 10 hr and the pharmacokinetic parameters were derived from the concentrations. After intravenous administration, the area under the plasma concentration time curve and plasma concentrations of acyclovir in group C were higher than in group A, while the volume of distribution and plasma clearance of acyclovir in group C were only 12.8% and 10.36% of those of group A, respectively. A similar trend was observed after oral administration. However, the bioavailability (F) of acyclovir was 8.4% in group A versus 1.5% in group C. In addition, the concentrations and kinetic parameters of valproic acid between the two groups after oral and intravenous administration were not different. In conclusion, co-administration of single doses of acyclovir and valproic acid led to reduced oral bioavailability of acyclovir, but increased concentrations of acyclovir due to reduced volume of distribution and clearance. These observations call for a cautious approach to the concomitant use of the two drugs until human studies are done.     

直肠给药吸收促进剂研究概况

本文就直肠给药吸收促进剂研究情况作一概述。简要介绍直肠给药的作用机制、影响直肠给药的因素，详细讨论常用的吸收促进剂性质和应用，比较了不同促进剂的特征和优缺点。     

Interaction between different doses of simvastatin after two-week administration and metoprolol injection on the heart rate in normocholesterolemic rats

Heart rate slowing is the beneficial effect after beta-blocker administration in cardiac heart failure and ischemic heart disease. However, bradycardia and another cardiac disturbances after beta-blockers therapy are the most dangerous side effects. Many patients with cardiovascular diseases receiving beta-blockers are recommended to statin therapy, as well. Previous study showed that statins may desensitize beta-adrenergic signaling, in cardiac myocytes via reduction of isoprenylation of G-protein gamma-subunits. The aim of the study was to evaluate the influence of simvastatin at different doses and metoprolol injection on the heart rate in normocholesterolemic rats. The experiments were performed in Wistar rats, outbred males. Simvastatin at 1, 10 or 20 mg/kg or vehicle (0.2% methylcellulose) were given intragastrically during two-week period. After two week administration of simvastatin, rats were injected intraperitoneally with metoprolol at 5 mg/kg b.w. The heart rate signals were provided by Isotec pressure transducer connected to a direct current bridge amplifier and catheter was implanted into the right carotid artery. No changes in the baseline heart rate among all groups of the animals were observed. Metoprolol administration caused statistically significant decrease in heart rate in all groups of rats. In the control group, after metoprolol administration heart rate slowed down to 83.11 +/- 1.11% (p < 0.05) of the baseline values, in group receiving simvastatin at 1 mg/kg b.w. 82.72 +/- 5.49% (p < 0.05), in group receiving simvastatin at 10 mg/kg b.w. 85.13 +/- 4.75 (p <0.05) and in group receiving simvastatin at 20 mg/kg b.w. 85.13 +/- 4,75% (p < 0.05) of the baseline values. No significant decrease in heart rate in the control group as compared to groups receiving simvastatin in different doses was observed. No significant changes among animals receiving simvastatin in different doses were observed, as well. CONCLUSION: Two week administration of simvastatin in different doses to normocholesterolaemic rats does not modify metoprolol-induced depressing influence on the heart rate.     

器官移植患者用药的药物相互作用

<正>由于器官移植技术、移植免疫基础以及各种免疫抑制剂的研究进展,器官移植已成为临床治疗器官功能衰竭的有效治疗手段。在器官移植中,不可避免地要将免疫抑制剂、抗感染药物以及其他维持     

The impact of an electronic prescribing and administration system on the safety and quality of medication administration

Objective To assess the effect of an electronic prescribing and administration system on the safety and quality of medication administration in a UK hospital. Setting Surgical ward in a teaching hospital. Method Data were collected before and after introducing a closed‐loop system comprising electronic prescribing, automated dispensing, barcode patient identification and electronic medication administration records (ServeRx, MDG Medical). We observed medication administration during drug rounds and assessed medication administration error (MAE) rates for ward‐stock and non‐ward‐stock drugs, accuracy of medication administration documentation, timeliness of administration, administration of medication from unlocked areas and supervision of patients taking oral medication by nursing staff. Key findings Pre‐ and post‐intervention MAE rates were 6.4 and 2.3% respectively for ward‐stock drugs (95% confidence interval for the difference (CI) ?5.8 to ?2.4%), and 14.6 and 13.7% for non‐ward‐stock drugs (CI ?6.5 to 4.7%). Excluding omissions due to unavailability, pre‐ and post‐intervention MAE rates were 6.2 and 2.2% respectively for ward‐stock drugs (CI ?5.7 to ?2.3%), and 9.2 and 3.5% for non‐ward‐stock drugs (CI ?9.3 to ?2.1%). Pre‐intervention, 2086 doses (96.3%) were documented correctly and 1557 (95.9%) post‐intervention (CI ?1.6 to 0.8%). There were five clinically significant documentation discrepancies pre‐intervention (0.2%), and 33 (2.0%) afterwards (CI 1.1 to 2.5%). Timeliness of administration improved post‐intervention (P < 0.001; Chi‐square test), as did administration of medication from unlocked areas (CI 4.7 to 7.3%) and supervision of patients taking oral medication (CI 17 to 23%). Conclusion Reductions in MAEs, excluding omissions due to unavailability, occurred for both ward‐stock and non‐ward‐stock drugs. The system also improved timeliness and security of drug administration. However, there was an increase in potentially significant documentation discrepancies.     

Effect of capsule colour and order of administration of hypnotic treatments

Summary Ninety-six hospitalized insomniac patients were asked to compare by a daily questionnaire the effect on sleep of the colour of the capsules and the order of administration of two treatments — heptabarbital and placebo. A balanced incomplete-block design was used; sleep onset time and sleep duration time were the main criteria of assessment. There was a significant interaction of colour and order of administration with sex. The placebo response was positive in 36% of instances.Research Associate     

Pharmacokinetics of pancuronium in man: A linear system

Summary Pancuronium in bolus doses of 40 to 350 µg/kg was administered to surgical patients in order to evaluate the linearity of its pharmacokinetics. The profile of the plasma decay curve and of its urinary elimination were compared with reference to the administered dose. It was possible to superimpose the dose-normalized plasma decay-curves. The parameters of the two compartment-open model used to describe the pharmacokinetics of pancuronium were not influenced by the dose. The elimination half-life was 89±20 min and the plasma clearance was 1.84±0.38 ml/min/kg. The profiles of cumulative urinary excretion were also dose-independent. After 6 and 24 h, 57% and 69% of the administered dose, respectively, had been excreted in the urine. The results indicate that the pharmacokinetics of pancuronium is linear.     

The neuromuscular and autonomic blocking activities of pancuronium,Org NC 45, and other pancuronium analogues,in the cat

Twenty-six mono-or bis-quaternary salts of 3,17-dioxy-2β,16β-dipiperidino-5α-androstanes (including pancuronium) and one 17-desoxy congener were tested for neuromuscular blocking and autonomic blocking activities in the chloralose-anaesthetized cat. The 17β-acetoxy series, all the members of which contain an acetylcholine-like fragment in the steroidal D-ring, was most selective for effecting neuromuscular blockade. The salient member of this series is 3α,17β-diacetoxy-2β,16β-dipiperidino-5α-androstane 16β-N-monomethobromide (Org NC 45) which is highly selective in blocking neuromuscular transmission in that a dose approximately sixty times greater than the neuromuscular blocking dose was required to block responses to vagal stimulation. In contrast, in doses sufficient to produce neuromuscular block, pancuronium simultaneously blocked responses to vagal stimulation. Moreover, pancuronium and Org NC 45 exhibited the same order of neuromuscular blocking activity and therefore the latter potentially represents a useful addition to the armamentarium of neuromuscular blocking agents currently in clinical use.     

Interaction between warfarin and nafcillin: case report and review of the literature

A 39-year-old man with a history of deep vein thrombosis and septic arthritis of the left knee was treated with warfarin and cefazolin. Therapeutic prothrombin times and international normalized ratios (INRs) were maintained with warfarin 32 mg/week for approximately 1 month. When the patient's antibiotic regimen was changed from cefazolin to nafcillin 2 g every 4 hours, his INR declined significantly. His warfarin dosage had to be increased to a maximum of 88 mg/week to achieve a therapeutic INR. After completion of antibiotic therapy with nafcillin, the patient's warfarin requirements slowly declined over several weeks. A maintenance dosage of warfarin 42-48 mg/week was necessary after nafcillin discontinuation. Hepatic cytochrome P450 isoenzyme induction by nafcillin is likely the mechanism of a warfarin-nafcillin interaction. The usual onset of effect is within 1 week after starting nafcillin, and the offset of the effect is usually evident within 4 weeks after nafcillin discontinuation. In patients taking warfarin who are prescribed nafcillin, a 2-4-fold increase in the warfarin dose may be necessary, and clinicians should closely monitor INRs.     

Chronic administration of verapamil, ketoconazole and carbamazepine: impact on immunological parameters

Inhibitors of P-glycoprotein (P-gp) (verapamil) or cytochrome P-450 (ketoconazole) may reduce IL2 production and T lymphocyte proliferation in vitro. We have examined the effects of chronic oral administration of these drugs and of the cytochrome P450 inductor, carbamazepine, on the hematological and immunological parameters of mice. We found no changes after giving the mice 0.12 mg verapamil, 0.85 mg ketoconazole, or 0.514 mg carbamazepine per mouse for 4 weeks (5 days/week). But giving the drugs for an additional 7 weeks at 0.6 mg (verapamil), 4.25 mg (ketoconazole) or 2.57 mg/mouse (carbamazepine), resulted in significant decreases in monocytes in the verapamil treated group (-51%) and in CD4+ cells in the carbamazepine group (-35%). Chronic oral administration of these drugs reduced the lymphocyte counts of mice by 10-18% and their NK counts by 10-16%. These changes could be due to changes in P-gp function in the transport of IL2, with decreases caused by verapamil and ketoconazole.     

Interaction between anticoagulants and contraceptives: an unsuspected finding

To assess the effects of oral contraceptives on anticoagulant treatment the prothrombin times of 12 patients were measured while they were taking both drugs simultaneously and while they were taking only anticoagulants. The mean prothrombin time ratio was significantly higher when patients were taking both drugs than when they were taking only anticoagulants and their doses of anticoagulant were significantly lower. During both periods most of the prothrombin values remained in the therapeutic range. These findings suggest that, contrary to the common belief that oral contraceptives diminish the effects of anticoagulants, contraceptives in fact potentiate the action of the anticoagulants.     

Interaction between Levothyroxine and Phenprocoumon: a case report

Several case reports have associated the combined use of thyroid drugs and oral anticoagulants, like coumarin, with overanticoagulation. However, this effect has never been described for phenprocoumon, a coumarin derivate that is widely prescribed in continental European countries and in Latin America. We describe a 62-year-old female who had an unexpectedly labile anticoagulation profile when levothyroxine (Puran T4®) was added to her drug therapy regimen, which included phenprocoumon (Marcoumar®). This resulted in an elevated international normalized ratio (INR) that was unrecordable and bleeding (macroscopic hematuria) that required hospitalization and treatment with vitamin K. The patient had been taking phenprocoumon for almost ten years for systemic embolism prophylaxis because of her history of mechanical bileaflet mitral valve prosthesis. One month before the events described, the patient was prescribed sodium levothyroxine (50 mcg daily) to treat hypothyroidism (TSH = 40 µU/mL; reference range, 0.40–4.0 µU/mL). Approximately 3 weeks prior to initiation of levothyroxine treatment, her INR was 2.8. A drug interaction was therefore suspected. The Horn Drug Interaction Probability Scale (DIPS) indicated a probable interaction between oral phenprocoumon and levothyroxine in this case. Clinicians should be aware that levothyroxine may interact with oral phenprocoumon, resulting in overanticoagulation.     

吸烟与药物相互作用

目的：探讨吸烟与药物的相互作用,指导临床合理用药。方法：检索国内外相关文献,进行分析与综述。结果：吸烟在药动学和药效学上与药物有相互作用。结论：临床应重视吸烟与药物的相互作用,确保用药安全。     

Interaction between frusemide and aspirin

• 1.1. The effects of the combination of aspirin and frusemide were studied on salicylate excretion by aspirin and on the diuresis and excretion of K⁺ and Na⁺ by frusemide in normal human subjects.
• 2.2. There was a paradoxical net reduction in the natriuresis induced by aspirin, from 29.4 ± 3.57 m-equiv and frusemide from 31.9 ± 1.27 to 23.7 ± 1.56 m-equiv on combined administration.
• 3.3. Frusemide caused a reduction of the kalliuretic effect induced by aspirin from 48.86 ± 8.36 to 18.3 ± 3.76 m-equiv.
• 4.4. The amount of salicylate excreted over a 3-hr period gave increases of 9.6 and 12.0% when aspirin was administered before frusemide and vice versa, respectively, while there was a 30.4% reduction when administered concomitantly.