Background: Physiologically based pharmacokinetic (PBPK) modeling is an established approach used in recent years for estimating drug disposition in challenging clinical scenarios where in vivo studies are difficult to perform. Metoclopramide is a benzamide derivative, widely indicated for its antiemetic and prokinetic actions. This study aims to develop a PBPK model for metoclopramide in infants to predict its systemic exposure in this population. Methods: To develop the model, a detailed literature review was conducted, and the required data related to the drug, human physiology, and published clinical studies were retrieved. After that, all information was integrated into the PK-Sim software, and the model was initially developed in adults to create a base; subsequently, it was extrapolated to infants. After successful development, these models were verified visually and numerically using visual predictive checks (VPCs), mean predicted-to-observed ratios (Rpre/obs), average fold error (AFE), and mean relative deviation (MRD). Results: All simulated profiles were consistent with observed data; computed AFE and Rpre/obs for key pharmacokinetic (PK) parameters, including area under the concentration-time curve from 0 to t (AUC0-t), maximum plasma concentration (Cmax), and clearance (CL), fell within an acceptable two-fold error range. Moreover, the MRD values for all profiles were <2, showing promising agreement between the reported and predicted datasets. Conclusions: The current model provides a robust framework to estimate the PK of metoclopramide in infants, which may help with dose individualization in this vulnerable population.

Paraneoplastic endocrine syndromes are well-recognised complications of lung malignancies, specifically small-cell lung cancer. The majority of patients with panhypopituitarism associated with lung cancer result from pituitary metastasis. In those with an enlarged pituitary stalk without obvious pituitary metastasis presenting with a combination of panhypopituitarism and arginine vasopressin deficiency (AVP-D), metastatic pituitary stalk infiltration should be considered rather than a paraneoplastic immune-mediated hypophysitis. We report a case of a 67-year-old gentleman with newly diagnosed lung adenocarcinoma, found to have panhypopituitarism before starting systemic anti-cancer treatment. Further hormonal tests revealed central hypothyroidism, hypogonadotropic hypogonadism and growth hormone deficiency. MRI of the pituitary demonstrated heterogeneous contrast enhancement without an obvious focal lesion. The pituitary stalk was slightly enlarged at the level of the optic chiasm, raising the possibility of hypophysitis. The patient was initiated on hydrocortisone and levothyroxine replacement therapy. Following hormone replacement, previously occult AVP-D became clinically apparent, manifesting as worsening dehydration, polyuria and polydipsia. The overnight water deprivation test confirmed AVP-D. The patient showed subsequent clinical improvement with desmopressin. Serum prolactin was mildly elevated, likely reflecting both pituitary stalk infiltration and concomitant metoclopramide therapy. This case discusses an exceptionally rare presentation of lung adenocarcinoma with isolated pituitary stalk infiltration, panhypopituitarism, and AVP-D before exposure to immune checkpoint inhibitors. Clinicians should be aware of this unusual manifestation, as prompt hormone replacement can significantly reduce morbidity and improve patient outcomes.

Cerebellar and medullary stroke can cause persistent nausea and vomiting that may be resistant to initial antiemetic monotherapy and interfere with oral intake and recovery. Evidence guiding management remains limited. We report a 48-year-old man with diabetes mellitus and acute-to-subacute infarcts involving the inferomedial right cerebellum and posterior right medulla who presented with 10 days of persistent nausea and vomiting accompanied by focal neurologic symptoms. Diabetic gastroparesis was considered, but abdominal imaging and gastric emptying scintigraphy did not support a contributory gastrointestinal cause. Ondansetron and metoclopramide provided only limited or temporary relief. Symptoms improved after sequential escalation to ondansetron, chlorpromazine, prochlorperazine, and amitriptyline; transdermal scopolamine was included in the discharge regimen. Nausea and vomiting were nearly resolved before discharge and fully resolved by three-month follow-up. Because multiple medications were introduced over a short interval and natural neurologic recovery may have contributed, the effect of any individual agent or combination cannot be determined. This case suggests that receptor-diverse pharmacotherapy may be considered when initial treatment fails while underscoring the need for further study of efficacy, safety, and medication sequencing.

Post-traumatic hiccups are an uncommon but distressing complication of traumatic brain injury (TBI), often resistant to conventional pharmacological agents, and the underlying mechanism may involve central neurological disruption of inhibitory pathways rather than gastrointestinal or metabolic aetiologies. We report a male patient in his early 30s who developed refractory hiccups following moderate TBI sustained in a high-impact motor vehicle collision; standard agents including chlorpromazine, metoclopramide, and haloperidol provided no meaningful relief after 48 h of combined treatment. Intravenous levetiracetam (1000 mg loading dose followed by 500 mg every 12 h) was initiated on hospital Day 6, which was followed by complete resolution of hiccups within 8 h; the patient was discharged on hospital Day 7 without recurrence and remained symptom-free at two-week outpatient follow-up. This case highlights levetiracetam as a promising rescue therapy for post-TBI hiccups refractory to conventional agents, possibly by modulating aberrant central neural circuitry, and further prospective studies are warranted to establish standardized treatment protocols for this challenging and underrecognised condition.

Microneedles have emerged as a promising technology for enhancing transdermal delivery. The micron-sized needles penetrate the stratum corneum with minimal pain and discomfort. Among the different microneedle types, hydrogel microneedles offer distinct advantages, including sustained drug release and biocompatibility. The present study aimed to optimize the formulation of hydrogel microneedles composed of Gantrez[®]S-97, a hydrophilic polymer, crosslinked with the sodium salt of hyaluronic acid at 80 °C to form a hydrogel matrix. Polyvinyl pyrrolidone, a synthetic water-soluble polymer, was incorporated to improve microneedles stability and enhance sustained drug release. Metoclopramide hydrochloride is a dopamine receptor antagonist with variable oral bioavailability and established clinical use in the management of chemotherapy-induced nausea, vomiting, and gastroesophageal reflux disorders. Metoclopramide-loaded hydrogel microneedle formulations were prepared with varying polymer compositions and evaluated by in vitro permeation studies. The optimized formulation demonstrated mechanical strength, uniform needle morphology, and a sustained drug release profile over 24 h. The hydrogel microneedles achieved up to an 18-fold enhancement in transdermal drug permeation compared to a conventional transdermal film.