nlmixr2llm

LLM-facing documentation for the nlmixr2 pharmacometric modeling ecosystem in R, distributed as an R package and as a Claude Code plugin.

The same content — a single combined nlmixr2verse agent plus per-package skill files for rxode2, nlmixr2, nonmem2rx, monolix2rx, and babelmixr2 — is shipped two ways:

As an R package, with accessor functions for use as a system prompt with any LLM client (ellmer, the Anthropic SDK, the OpenAI SDK, …) and installers that write the files into the locations expected by Claude Code, OpenAI Codex CLI, Positron Assistant, and other tools that follow the AGENTS.md convention.
As a Claude Code plugin via the .claude-plugin/ directory at the repo root, so users who already use the Claude Code plugin marketplace can install without touching R.

Coverage

A single combined nlmixr2verse agent spans the whole ecosystem (the orchestration layer), and each package ships a skill for on-demand depth:

Package	Skill	Purpose
`rxode2`	✓	ODE-based PK/PD modeling and simulation
`nlmixr2`	✓	Population PK/PD parameter estimation (SAEM, FOCEi, …)
`nonmem2rx`	✓	Convert finished NONMEM runs into rxode2 / nlmixr2 objects
`monolix2rx`	✓	Convert Monolix projects into rxode2 / nlmixr2 objects
`babelmixr2`	✓	Fit nlmixr2 models via NONMEM, Monolix, or PKNCA backends

The nlmixr2verse agent covers all five packages and the end-to-end workflow that connects them (author in rxode2 → fit in nlmixr2 → run on other engines with babelmixr2 → import legacy runs with nonmem2rx / monolix2rx).

Install (R package)

# install.packages("remotes")
remotes::install_github("john-harrold/nlmixr2llm")

Usage

Use as a system prompt with any LLM client

library(nlmixr2llm)

prompt <- system_prompt(packages = c("rxode2", "nlmixr2"))

# Example: with ellmer
chat <- ellmer::chat_anthropic(system_prompt = prompt)
chat$chat("Write a one-compartment PK model with first-order absorption in rxode2.")

Install into Claude Code

# User-level (~/.claude/agents/, ~/.claude/skills/)
install_claude_code(scope = "user")

# Or project-local (.claude/agents/, .claude/skills/) under the current project
install_claude_code(scope = "project")

Install into OpenAI Codex CLI

# Project AGENTS.md at the repo root
install_codex(scope = "project", packages = c("rxode2", "nlmixr2"))

# Global ~/.codex/AGENTS.md
install_codex(scope = "user", mode = "append")

Codex enforces a default 32 KiB cap on combined AGENTS.md content. The full corpus (~62 KiB) exceeds that. The combined nlmixr2verse agent is ~29 KiB on its own and is included whole whenever agents are requested, so packages = ... only subsets the skills. For Codex, install include = "agents" (just the agent, ~29 KiB) or include = "skills" with a packages = ... subset.

Install into Positron Assistant

# Project-root agents.md (also picked up by Codex, Cursor, Aider, Zed, ...)
install_positron(workspace = ".", style = "agents_md")

# Per-package .github/instructions/*.instructions.md with applyTo: "**/*.R"
install_positron(workspace = ".", style = "instructions")

Install for any tool that reads `AGENTS.md`

install_agents_md(path = ".", packages = c("rxode2", "nlmixr2"))

Covered by the agents.md cross-tool spec: Codex, Cursor, Aider, GitHub Copilot, Zed, Warp, Jules, Devin, and others.

Keeping installs in sync

The installers write independent copies, so re-run them after upgrading the package (pass overwrite = TRUE / mode = "write" to refresh existing files). install_claude_code() and install_positron(style = "instructions") keep a manifest (.nlmixr2llm-manifest) and, by default (prune = TRUE), remove files they installed in an earlier version but no longer ship — so a renamed agent or dropped package doesn’t leave an orphan behind. Only files nlmixr2llm created are ever removed.

To check whether your installed content is current without reinstalling, run nlmixr2llm_status() — it inspects every install target (Claude Code user/project, Codex / AGENTS.md, and both Positron styles), reports any files that are out of date, and prints the refresh command for each. The nlmixr2verse agent also runs this check itself once per session and tells you when a refresh is available.

When you load the package interactively (library(nlmixr2llm)), it runs this check automatically (read-only) and prints a one-line notice if any installed copy is out of date — staying silent otherwise. Disable it with options(nlmixr2llm.startup_check = FALSE).

Use as a Claude Code plugin (no R required)

The bundled plugin manifest lives in .claude-plugin/ at the repo root (pointing at the same inst/agents/ and inst/skills/ content the R package uses) so the repo doubles as a plugin source:

/plugin marketplace add john-harrold/nlmixr2llm
/plugin install nlmixr2llm@nlmixr2llm

API

Function	Purpose
`list_packages()`, `list_agents()`, `list_skills()`	Discovery
`get_agent()`, `get_skill(pkg)`	Raw markdown (`get_agent()` returns the combined `nlmixr2verse` agent)
`system_prompt(packages, include)`	Combined prompt for LLM clients
`install_claude_code(scope, packages, ...)`	Claude Code skill/agent tree
`install_codex(scope, packages, mode, include)`	Codex CLI `AGENTS.md`
`install_agents_md(path, packages, ...)`	Project-root `AGENTS.md` for any `agents.md`-aware tool
`install_positron(workspace, style, packages, ...)`	Positron Assistant instructions
`nlmixr2llm_status(path)`	Report whether installed files (Claude Code, Codex, Positron) are out of date vs the package

Layout

nlmixr2llm/
├── DESCRIPTION
├── NAMESPACE
├── LICENSE
├── R/
│   ├── content.R
│   ├── claude_code.R
│   ├── codex.R
│   ├── agents_md.R
│   └── positron.R
├── man/
├── .claude-plugin/        # Claude Code plugin manifest (not shipped in R tarball)
└── inst/
    ├── agents/
    └── skills/

Contributing

The skill and agent files are plain Markdown with YAML frontmatter — edit them in inst/agents/ and inst/skills/. Vignette references point at filenames in each package’s source repo (github.com/nlmixr2/<pkg>/tree/main/vignettes/); please verify any new references against the live repo before merging.

License

BSD 3-Clause. See LICENSE.