Fumiya Tomonaga

Influence of circadian-stage-dependent dosing schedule on nephrotoxicity and pharmacokinetics of isepamicin in rats.

Nephrotoxicity was more marked in rats receiving isepamicin at midlight than at middark. And, the once-daily administration at middark induced a lesser degree of nephrotoxicity than the twice-daily injection, which indicates that the once-daily treatment therapy may have potential value in the clinical use of aminoglycosides. Images

Pharmacokinetic Analysis of Mannitol in Relation to the Decrease of ICP

Mannitol has been used for the reduction of raised intracranial pressure (ICP) for years, however, the most effective dose and the method of administration have remained controversial [2, 3]. One of the reasons is that the pharmacokinetics of mannitol has not been clearly understood in relation to the changes of mannitol concentration and serum osmolality and the decrease of ICP after the mannitol administration [1].

Pharmacokinetic Study of Mannitol in Subjects with Increased ICP

Six human subjects received mannitol as an intravenous dip (DIV) infusion. In each subject, the concentration of mannitol and serum osmolality were rapidly elevated during mannitol administration and reached the maximum at the end of mannitol administration. Then, it exponentially decreased. There was a strong positive correlation between mannitol concentration and extrinsic serum osmolality. The integrated values of mannitol concentration difference between the central (Cc) and the peripheral compartment (Pc) correlated with the changes of ICP reduction during mannitol administration. The results indicate that the changes of ICP reduction depend on the mannitol concentration difference between Cc and Pc.

Pharmacokinetics and Pharmacodynamics of Serum Glycerol in Patients with Brain Edema: Comparison of Oral and Intraveneous Administration

To clarify the pharmacokinetics and effect of ICP reduction of glycerol administered orally, the serum concentration of glycerol was measured by the enzymatic method and ICP was measured by the subdural balloon method in severe head injured patients with brain edema and increased ICP. Sequential change of serum glycerol concentration and its relationship to the reduction of ICP were analyzed. The results showed that the pharmacokinetics of glycerol through oral administration were similar to that of intravenous glycerol administration and the changes of ICP were also similar to that of intravenous glycerol administration. We determined that glycerol can be administered either per oral or per venous to obtain the same results for treatment of brain edema with raised ICP.

Determination of Serum Mexiletine Concentrations and its Protein Binding by High-performance Liquid Chromatography.

A new method to determine serum mexiletine (MX) concentrations using high-performance liquid chromatography (HPLC) was established.This method could reduce a sample volume to 100μ1 of serum and could shorten the pretreatment time to less than 10 minutes by using Chem Elut minicolumn. The results obtained by this method (n=28) correlated well with those obtained by gas chromatography method (r=0.997).Moreover, this method had a good recovery and reproducibility, suggesting that it is an excellent method for determining serum MX concentrations.Using this HPLC method, serum protein binding of MX was studied in healthy subjects and patients with chronic renal failure (CRF). The protein binding of MX was 60.83±4.37% in healthy subjects (n=6) and 52.45±6.22% in CRF (n=9).The protein binding of MX in CRF was significantly decreased, compared with healthy subjects, indicating an apparent elevation of free drug concentrations.In general, dose adjustment of MX in CRF is considered to be unnecessary. However, free drug concentrations may participate in the appearance of effects and adverse reactions. The possibility of enhanced pharmacological effects and increased adverse reactions due to such variations of protein binding in CRF should be also considered.

A Study of the Concentration of Mannitol for the Treatment of Raised ICP

Mannitol is a well known hypertonic agent for the control of raised intracranial pressure (ICP). However, the most effective method of administration of mannitol has not yet been established. In this paper, the authors made 10%, 20%, and 30% of mannitol and set volume and rate of administration of mannitol, in an attempt to clarify the most effective method of mannitol administration to obtain the lowest and the longest reduction of raised ICP.

Awareness of pharmacy students about the practical training at hospital pharmacies.

A questionnaire was used to ascertain the awareness of pharmacy students (below: p.students) about the practices and business in their field at hospitals.The subjects of this survey were 513 p.students who had participated in practical training at the Pharmacy Department of Kitasato University Hospital during the last 5 years.1.Most of the students participated in practical training at hospital pharmacies were hoping to become hospital pharmacists, and their experience through the practical training was a basis for their choice of occupation.2.Their comprehensions of pharmacist and job content at hospital pharmacies were low. 3.Through their experience at hospital pharmacies, most students realized the heavy responsibility of pharmacists and the necessity of applied pharmaceutical knowledge. 4.It is necessary to add practical training at hospital to the curriculam at pharmacy school for students hoping to work at hospital pharmacies.5.Cooperation of the specialists in this field is expected to reduce the heavy duty of the pharmacists at the hospital.

Stability of Aminoglycoside Antibiotics in Anemopathy

Stability of aminoglycosides (AG) in anemopathy was investigated in regard to change in appearance and in pH, smell and residual potency by compatibility tests using Alevaire, and influence of ultrasonic nebulization. In this study, commercially available injections of gentamicin (GC), kanamycin (KC), streptomycin (SC), amikacin (BK), dibekacin (PM) and tobramycin (TC) were used. The results are summarized as follows:1) No changes in appearance and pH were observed in all the solutions of AG mixed with Alevaire. BK and PM kept primary potency for 168 hours after mixing, but the potency of GC began to decrease 24 hours after, and also that of KC, SC and TC decreased slightly 6 to 168 hours after. 2) AG was stable even under the influence of ultrasonic nebulization, though a bad smell was given out from additives in AG injections due to their decomposition.From these results, it is emphasized that: 1) AG should be mixed just before use, and 2) attention should be paid to odor and taste, as well as residual potency.

Study on Compatibility of Urokinase with Other Drugs

Compatibility tests on Urokinase (UK) with 39 kinds of drugs prescribed in combination with UK in our hospital were performed in terms of visible change, pH and residual potency of UK as determined by fibrin-plate method after the mixture. The results may be summarized as follows:determined by fibrin-plate method after the mixture. The results may be summarized as follows:1) Mixture of UK and Calcicol or Persantin showed precipitation immediately after mixing, while mixture of UK and Keflin, K. C. L., Penbritin or Celtol showed a decrease in potency 0-3 hours after mixing. Therefore, these mixtures are incompatible.2) Mixture of UK and Solita T3, Pydoxal, Vitamedin, Vitaneurin, MDS or Novoheparin showed a decrease in potency 6 hours after mixing. Hence these mixtures should be made carefully.

Compatibility of Commercial Gentamicin Injection with Six Drugs for Inhalation

Compatibility of commercial gentamicin injection (GC) with six drugs for inhalation (Alevaire, Bisolvon, Asthone, Asthpul, Alotec and Venetlin) was investigated on 15 models of mixture in terms of change in appearance, pH and residual potency in microbioassay. It was found that in all these models the potency of GC deteriorated 0-3 days after mixture.