Synthesis, Characterization and Preliminary Anticancer Study of Novel 5-fluorouracil Conjugate with Pyrrolidine Dithiocarbamate as a Mutual Anticancer Prodrug

5-Fluorouracil is one of the commonly used chemotherapy drugs in anticancer therapy; unfortunately treatment with 5-FU by solely has many drawbacks low lipophilicity, low permeability, low molecular weight, and its relatively poor plasma protein binding; also a brief half-life therefore frequent administration is required to maintain the optimal therapeutic plasma level which in addition to its poor selectivity, drug resistance and limited penetration to cancer cells; leads to increased incidence of side-effects to healthy cells/tissues and low response rates. In order to minimize these drawbacks; 5-FU was chemically conjugated with pyrrolidine dithiocarbamate (PDTC) in a mutual prodrug moiety (S-(9H-purin-6-yl) 3-((pyrrolidine-1-carbonothioyl)thio)propanethioate) "compound [IV]" with (chloroacetic acid) and (chloroethanol) being the linkers ;synthesized prodrug and intermediates were characterized and identified using FTIR ,1H NMR and all the results shown good agreements with the proposed chemical structures of the synthesized compounds. ; in-vitro preliminary cytotoxicity study was conducted for compound [IV] and 5-FU on CAL 51 and B16V cell lines ,results showed enhanced cytotoxic effects for [IV] over 5-FU.

Accidental Overdose of Paliperidone Palmitate

Long-acting injectable (LAI) antipsychotics first introduced in 1960s are useful in the treatment of schizophrenic patients with poor medication adherence due to their maintaining feature of therapeutic plasma level without daily administration. Paliperidone Palmitate is one of such LAI antipsychotic drugs used due to its benefit of maintaining a therapeutic plasma level with four-week interval of injections. We report the case of a 21-year-old male with a history of mental illness that presented with selective mutism, disorganized speech, thought process and behavior, and auditory hallucinations who accidentally received 624 mg Paliperidone Palmitate intramuscularly with no reported side effects after 2 weeks of monitoring and observation. Paliperidone is a D2, 5HT2A receptor antagonist with additional antagonist activity at α-1 and α-2, H-1 receptor sites, and four metabolic pathways identified for its metabolism. Studies have reported adverse effects such as acute dystonia, acute renal failure, and cardiovascular abnormalities with Paliperidone overdose; however there is no reported literature on Paliperidone Palmitate overdose, though there have been reported cases of Paliperidone Palmitate side effects of hypersexuality and angioedema with the standard dose.

Short-term variation in plasma mitotane levels confirms the importance of trough level monitoring

ObjectiveMitotane is the drug of choice in patients with adrenocortical carcinoma. The anti-neoplastic effect is correlated with mitotane plasma levels, which render it crucial to reach and maintain the concentration above 14 mg/l. However, mitotane pharmacokinetics is poorly understood. The aim of this study was to investigate the variation in plasma mitotane levels during the day and the influence of a single morning dose.DesignA prospective case–control study was conducted to investigate the variation in plasma mitotane levels.MethodsPatients who had been treated for at least 24 weeks and had reached the therapeutic plasma level (14 mg/l) at least once were eligible. In the first group, mitotane levels were determined hourly for the duration of 8 h after administration of a single morning dose. In the second group, mitotane levels were assessed similarly without administration of a morning dose.ResultsTen patients were included in this study, and three patients participated in both groups. Median plasma level at baseline was 16.2 mg/l (range 11.3–23.3 mg/l) in the first group (n=7) and 17.0 mg/l (13.7–23.8) in the second group (n=6). Plasma levels displayed a median increase compared with baseline of 24% (range 6–42%) at t=4 after morning dose and a change of 13% (range −14 to 33%) at t=4 without morning dose (P=0.02).ConclusionA substantial increase in mitotane plasma levels was observed in steady-state patients within a period of 8 h after morning dosing. Without morning dose, mitotane curves showed a variable profile throughout the day. This implies that random sampling could yield incidentally high levels. For this reason, we recommend early-morning trough sampling as standard management in monitoring mitotane treatment.

Valproate as prophylaxis for clozapine-induced seizures: survey of practice

Aims and MethodTo evaluate the prescribing of valproate in clozapine-treated individuals who may be at risk of seizure. We collected point-prevalent clinical characteristics and demographics of all in-patients prescribed clozapine in an acute mental health trust. Data were collected from case notes, electronic records and drug charts, and analysed against a set audit standard.ResultsData were collected for 81 in-patients. Of all deemed to be at risk of seizure (n=37) only 24% were prescribed valproate at a therapeutic plasma level.Clinical ImplicationsThe majority of patients prescribed clozapine at risk of seizures were not adequately protected from this risk. Clear guidelines are required.